Tacrolimus drug concentration rapid detection device based on micro-fluidic chip

Abstract

The invention relates to the field of drug concentration detection, in particular to a rapid tacrolimus drug concentration detection device based on a micro-fluidic chip. The detection device comprises a blood sampling area, a separation area, a liquid medicine storage area, a waste liquid storage area and a spectrograph, the separation area is used for separating a tacrolimus medicine in a blood sample solution, and a liquid medicine sample and a waste liquid sample are obtained; the spectrograph is used for collecting liquid medicine spectral data of the liquid medicine sample in the liquid medicine storage area and waste liquid spectral data of the waste liquid sample in the waste liquid storage area, and detecting the concentration of the tacrolimus medicine in the blood sample solution according to the liquid medicine spectral data and the waste liquid spectral data. According to the invention, the accuracy of detecting the concentration of the tacrolimus drug in the blood can be improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of drug concentration detection, in particular to a tacrolimus drug concentration rapid detection device based on a microfluidic chip. BACKGROUND

[0002] Microfluidic chip technology is a kind of miniaturized platform based on micron channel and micro processing technology, which realizes the integration and automation of traditional laboratory functions by accurately controlling and analyzing fluid, and its basic principle is to use micro fluid mechanics principle to control fluid through micro channel, micro valve and micro pump, etc. Components realize sample separation, mixing, transmission, detection and other functions, tacrolimus is a kind of strong immunosuppressant, mainly used for preventing rejection after organ transplantation, and its pharmacological effect depends on the combination with plasma protein, so as to play the immune suppression effect.

[0003] In related technologies, the spectral data of blood samples containing tacrolimus drugs is usually collected, and the tacrolimus drug concentration is detected by using the spectral data, but because tacrolimus drugs will combine with red blood cells and plasma proteins in blood, the combined product will interfere with the collected spectral data, thereby reducing the accuracy of detecting the tacrolimus drug concentration in blood. SUMMARY

[0004] In order to solve the technical problem that the product combined with tacrolimus drugs, red blood cells and plasma proteins will interfere with the spectral data, thereby reducing the accuracy of detecting the tacrolimus drug concentration in blood, the purpose of the present application is to provide a tacrolimus drug concentration rapid detection device based on a microfluidic chip, and the technical solution adopted is as follows: The present application provides a tacrolimus drug concentration rapid detection device based on a microfluidic chip, the detection device comprises a blood collection area, a separation area, a drug liquid storage area, a waste liquid storage area and a spectrometer, the separation area is used for separating tacrolimus drugs in blood sample solution, and obtaining drug liquid sample and waste liquid sample, the spectrometer is used for collecting drug liquid spectral data of drug liquid sample in drug liquid storage area and waste liquid spectral data of waste liquid sample in waste liquid storage area, and detecting the tacrolimus drug concentration in blood sample solution according to the drug liquid spectral data and the waste liquid spectral data, wherein the method for detecting the tacrolimus drug concentration in blood sample solution comprises: According to the difference between the reflectance intensity of the same wavelength in the drug solution spectrum data and the waste liquid spectrum data, an initial wavelength is screened out; the standard reflectance intensity of a plurality of characteristic wavelengths is obtained from the standard spectrum diagram of the tacrolimus drug component, and according to the distance between each initial wavelength and the characteristic wavelength, a reference characteristic wavelength of each initial wavelength is obtained; according to the difference between each initial wavelength and the reference characteristic wavelength and the reflectance intensity of the same initial wavelength in the drug solution spectrum data and the waste liquid spectrum data, an effective degree of each initial wavelength is obtained; based on the effective degree, a wavelength to be analyzed is screened out from all the initial wavelengths; According to the difference between the reflectance intensity of the same wavelength in the drug solution spectrum data and the waste liquid spectrum data, an initial wavelength is screened out; the standard reflectance intensity of a plurality of characteristic wavelengths is obtained from the standard spectrum diagram of the tacrolimus drug component, and according to the distance between each initial wavelength and the characteristic wavelength, a reference characteristic wavelength of each initial wavelength is obtained; according to the difference between each initial wavelength and the reference characteristic wavelength and the reflectance intensity of the same initial wavelength in the drug solution spectrum data and the waste liquid spectrum data, an effective degree of each initial wavelength is obtained; based on the effective degree, a wavelength to be analyzed is screened out from all the initial wavelengths; According to the difference between the reflectance intensity of the same wavelength in the drug solution spectrum data and the waste liquid spectrum data, an initial wavelength is screened out; the standard reflectance intensity of a plurality of characteristic wavelengths is obtained from the standard spectrum diagram of the tacrolimus drug component, and according to the distance between each initial wavelength and the characteristic wavelength, a reference characteristic wavelength of each initial wavelength is obtained; according to the difference between each initial wavelength and the reference characteristic wavelength and the reflectance intensity of the same initial wavelength in the drug solution spectrum data and the waste liquid spectrum data, an effective degree of each initial wavelength is obtained; based on the effective degree, a wavelength to be analyzed is screened out from all the initial wavelengths;

[0005] Further, the screening of the initial wavelength comprises: The absolute value of the difference between the reflectance intensity of the same wavelength in the drug solution spectrum data and the waste liquid spectrum data is normalized to obtain the reflectance intensity difference value between the drug solution spectrum data and the waste liquid spectrum data at each wavelength; The wavelength with the reflectance intensity difference value greater than the preset difference threshold value is taken as the initial wavelength.

[0006] Further, the reference characteristic wavelength of each initial wavelength comprises: Any one initial wavelength is taken as a target initial wavelength, and the absolute value of the difference between the target initial wavelength and each characteristic wavelength is taken as the distance parameter between the target initial wavelength and each characteristic wavelength; The characteristic wavelength corresponding to the minimum value of the distance parameter is taken as the reference characteristic wavelength of the target initial wavelength.

[0007] Further, the effective degree of each initial wavelength comprises: The distance parameter between the target initial wavelength and the reference characteristic wavelength is negatively correlated to obtain the first effective coefficient of the target initial wavelength; The average value of the reflectance intensity of the target initial wavelength in the drug solution spectrum data and the waste liquid spectrum data is taken as the second effective coefficient of the target initial wavelength; The effective degree of the target initial wavelength is obtained by synthesizing and normalizing the first effective coefficient and the second effective coefficient.

[0008] Further, the filtering of the to-be-analyzed wavelengths from all the initial wavelengths comprises: The initial wavelength with the effective degree greater than the preset effective threshold is taken as the to-be-analyzed wavelength.

[0009] Further, the obtaining of the relative intensity coefficient of each to-be-analyzed wavelength in the waste liquid spectrum data comprises: The numerator is the reflected light intensity of each to-be-analyzed wavelength in the waste liquid spectrum data, and the denominator is the standard reflected light intensity of the reference characteristic wavelength of each to-be-analyzed wavelength, and the ratio is taken as the relative intensity coefficient of each to-be-analyzed wavelength in the waste liquid spectrum data.

[0010] Further, the obtaining of the regression weight of each to-be-analyzed wavelength in the waste liquid spectrum data comprises: Taking any one to-be-analyzed wavelength as a target to-be-analyzed wavelength, the difference between the relative intensity coefficients between the target to-be-analyzed wavelength and each other to-be-analyzed wavelength except the target to-be-analyzed wavelength in the waste liquid spectrum data is obtained to obtain the stability coefficient of the target to-be-analyzed wavelength in the waste liquid spectrum data. The regression weight of the target to-be-analyzed wavelength in the waste liquid spectrum data is obtained by synthesizing and normalizing the stability coefficient of the target to-be-analyzed wavelength in the waste liquid spectrum data and the effective degree of the target to-be-analyzed wavelength, and the cumulative value of the regression weights of all the to-be-analyzed wavelengths in the waste liquid spectrum data is equal to the numerical value 1.

[0011] Further, the obtaining of the stability coefficient of the target to-be-analyzed wavelength in the waste liquid spectrum data comprises: The absolute value of the difference between the relative intensity coefficients between the target to-be-analyzed wavelength and each other to-be-analyzed wavelength except the target to-be-analyzed wavelength in the waste liquid spectrum data is taken as the relative intensity difference value between the target to-be-analyzed wavelength and each other to-be-analyzed wavelength in the waste liquid spectrum data. The cumulative value of the relative intensity difference values between the target to-be-analyzed wavelength and all the other to-be-analyzed wavelengths in the waste liquid spectrum data is negatively correlated to obtain the stability coefficient of the target to-be-analyzed wavelength in the waste liquid spectrum data.

[0012] Further, the obtaining of the heparin drug concentration in the blood sample solution comprises: The reflected light intensity of each to-be-analyzed wavelength in the drug solution spectrum data, and the product value of the reflected light intensity of each to-be-analyzed wavelength in the waste liquid spectrum data and the regression weight are input into the weighted regression model, and the heparin drug concentration in the blood sample solution is output by the weighted regression model.

[0013] Further, the detection device further comprises a water electromagnetic magnet and a red blood cell wall breaking area, the water electromagnetic magnet is used for separating red blood cells in the blood sample solution, and the red blood cell wall breaking area is used for wall breaking treatment on the red blood cells separated by the water electromagnetic magnet.

[0014] The present application has the following advantages: The present application considers that the product of the combination of the tacrolimus medicine and the red blood cells and the plasma protein in the blood will cause interference to the spectrum data, thereby reducing the accuracy of the detection of the tacrolimus medicine concentration in the blood, so firstly, the separation area of the detection device is used to separate the tacrolimus medicine in the blood sample solution to obtain a medicine liquid sample and a waste liquid sample, considering that there may be incomplete separation, so that the tacrolimus medicine is contained in the two samples, in order to improve the accuracy of the detection of the tacrolimus medicine concentration in the blood, the present application uses the spectrometer in the detection device to collect spectrum data of the medicine liquid sample and the waste liquid sample to obtain medicine liquid spectrum data and waste liquid spectrum data, and preliminarily screens the initial wavelength related to the tacrolimus medicine, then the effective degree of the obtained spectrum data of the medicine liquid spectrum data and the waste liquid spectrum data at the same initial wavelength can reflect the degree that the spectrum data can represent the tacrolimus medicine, and further screening the to-be-analyzed wavelength which can more represent the tacrolimus medicine, improves the accuracy of the subsequent detection of the medicine concentration, considering that the content of the tacrolimus medicine in the waste liquid sample is less, if the reflection light intensity of the waste liquid spectrum data at the to-be-analyzed wavelength is directly used for regression analysis in the subsequent, the calculation result will be distorted, so the present application carries out weighted regression analysis on the reflection light intensity of the medicine liquid spectrum data and the waste liquid spectrum data at each to-be-analyzed wavelength by using the regression weight of the waste liquid spectrum data at each to-be-analyzed wavelength, so as to accurately calculate the tacrolimus medicine concentration in the blood sample solution, and improve the accuracy of the detection of the tacrolimus medicine concentration in the blood. BRIEF DESCRIPTION OF DRAWINGS

[0015] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, and the advantages thereof, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced as follows. Obviously, the drawings in the following description are only some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained without creative labor based on these drawings.

[0016] Fig. 1 The overall structure diagram of a tacrolimus medicine concentration rapid detection device based on a microfluidic chip provided by an embodiment of the present application; Fig. 2 The separation area structure diagram in a tacrolimus medicine concentration rapid detection device based on a microfluidic chip provided by an embodiment of the present application; Fig. 3A microfluidic chip-based tacrolimus drug concentration rapid detection method flow chart provided by one embodiment of the present application.

[0017] Reference signs: 1-blood collection area, 2-water solenoid, 3-red blood cell wall breaking area, 4-drug solution storage area, 5-waste liquid storage area, 6-catheter, 7-separation area, 8-drug solution outlet, 9-waste liquid outlet. DETAILED DESCRIPTION

[0018] In order to further illustrate the technical means and effects taken by the present application to achieve the predetermined object of the present application, the specific embodiments, structure, features and effects of a microfluidic chip-based tacrolimus drug concentration rapid detection device according to the present application are described in detail as follows. In the following description, different "one embodiment" or "another embodiment" do not necessarily refer to the same embodiment. In addition, the specific features, structures or characteristics in one or more embodiments can be combined in any suitable form.

[0019] 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 the present application belongs.

[0020] The specific scheme of the microfluidic chip-based tacrolimus drug concentration rapid detection device provided by the present application is described in detail below with reference to the accompanying drawings.

[0021] Please refer to Figs. 1-2respectively show the overall structure diagram of a microfluidic chip-based tacrolimus drug concentration rapid detection device and the separation region structure diagram provided by an embodiment of the application. The blood sample solution collected from a patient is first placed in the blood collection region 1. The liquid sample solution in the blood collection region 1 flows along the conduit 6. Since the tacrolimus drug combines with the red blood cells and plasma proteins in the blood, the combined product will interfere with the collected spectral data. During the flow process, the red blood cells in the blood sample solution are first separated by using the magnetic field generated by the water electromagnet 2. The separated red blood cells enter the red blood cell wall breaking region 3. In the red blood cell wall breaking region 3, the red blood cell wall can be broken by, for example, chemical drug surfactant Triton X-100. Then the blood sample solution carrying the broken red blood cells enters the separation region 7. Since the tacrolimus drug is hydrophobic, in the separation region 7, the tacrolimus drug, the red blood cells and the plasma proteins in the blood are separated by using a solvent that is not soluble in water but can dissolve the tacrolimus drug, such as ethyl oleate solvent. Thus, the liquid sample and the waste liquid sample are obtained. The liquid sample passes through the liquid outlet 8 to the liquid storage region 4, and the waste liquid sample passes through the waste liquid outlet 9 to the waste liquid storage region 5. Then the liquid spectral data of the liquid sample in the liquid storage region 4 and the waste liquid spectral data of the waste liquid sample in the waste liquid storage region 5 are collected by using a spectrometer, and the tacrolimus drug concentration in the blood sample solution is detected according to the liquid spectral data and the waste liquid spectral data. In an embodiment of the application, Raman spectrum is selected for tacrolimus drug concentration analysis, which is not limited herein.

[0022] Please refer to Fig. 3 which shows a microfluidic chip-based tacrolimus drug concentration rapid detection method flowchart provided by an embodiment of the application, including: Step S1: According to the difference in the reflected light intensity at the same wavelength between the liquid spectral data and the waste liquid spectral data, an initial wavelength is selected. The standard reflected light intensity of a plurality of characteristic wavelengths is obtained from the standard spectrum diagram of the tacrolimus drug component. According to the distance between each initial wavelength and the characteristic wavelength, the reference characteristic wavelength of each initial wavelength is obtained. According to the difference between each initial wavelength and the reference characteristic wavelength, and the reflected light intensity at the same initial wavelength between the liquid spectral data and the waste liquid spectral data, the effective degree of each initial wavelength is obtained. Based on the effective degree, the to-be-analyzed wavelength is selected from all the initial wavelengths.

[0023] Due to the problem of incomplete separation of the tacrolimus drug in the blood sample solution in the above operation, the drug solution sample contains a large amount of tacrolimus drug and a small amount of impurities, while the waste liquid sample contains a small amount of tacrolimus drug and a large amount of impurities, where the impurities refer to components such as plasma protein, hemoglobin, and albumin in the blood. Therefore, for the wavelength representing the tacrolimus drug components, the difference in the reflected light intensity at the same wavelength between the drug solution spectral data and the waste liquid spectral data is relatively large. Therefore, the embodiment of the present invention first preliminarily screens out the initial wavelength representing the tacrolimus drug components based on the difference in the reflected light intensity at the same wavelength between the drug solution spectral data and the waste liquid spectral data.

[0024] Preferably, in one embodiment of the present invention, the method for obtaining the initial wavelength specifically includes: The absolute value of the difference in reflected light intensity between the liquid spectral data and the waste liquid spectral data at the same wavelength is normalized, and the calculation result is limited to range, thereby obtaining the difference value of the reflected light intensity at each wavelength between the liquid spectral data and the waste liquid spectral data.

[0025] In one embodiment of the present invention, the normalization processing can be specifically, for example, maximum and minimum value normalization processing, and the normalization in subsequent steps can all adopt maximum and minimum value normalization processing. In other embodiments of the present invention, other normalization methods can be selected according to the specific range of numerical values, which will not be repeated here.

[0026] As an example, in one embodiment of the present invention, the expression for the difference in reflected light intensity at each wavelength between the liquid medicine spectrum data and the waste liquid spectrum data can be specifically, for example, as follows: in, Indicates the difference between the chemical solution spectrum data and the waste liquid spectrum data. The difference in reflected light intensity at each wavelength; Indicates that the spectral data of the drug solution is The intensity of reflected light at each wavelength; Indicates that the waste liquid spectrum data is The intensity of reflected light at each wavelength; Represents the normalization function, used for normalization processing.

[0027] The greater the difference in the reflected light intensity at a certain wavelength, the greater the difference in the content of the same component represented by the liquid sample and the waste liquid sample at that wavelength, and thus the more likely that the wavelength is the wavelength representing the tacrolimus drug component. Therefore, the wavelength with a reflected light intensity difference greater than a preset difference threshold can be used as the initial wavelength, where the preset difference threshold has a value range of In an embodiment of the present application, the preset difference threshold is set to 0.6, and the specific value of the preset difference threshold can also be set by the implementer according to the specific implementation scene, which is not limited herein.

[0028] Since the difference in the tacrolimus drug content between the drug sample and the waste sample is large, and the difference in the impurity content between the two is also large, in the obtained initial wavelengths, not only the wavelengths representing the tacrolimus drug component are contained, but also the wavelengths representing the impurity component are contained, therefore, the embodiment of the present application first obtains the standard reflection light intensity of a plurality of characteristic wavelengths from the standard spectrum diagram of the tacrolimus drug component, wherein the standard spectrum diagram of the tacrolimus drug component can be obtained from a database, the characteristic wavelengths of the tacrolimus drug component and the standard reflection light intensity of each characteristic wavelength are known data, for example, 1557 , 1648 and 1342 , etc. are characteristic wavelengths of the tacrolimus drug component.

[0029] Since the drug sample and the waste sample both contain impurities, which will cause certain interference to the corresponding spectrum data, such as the shift of the characteristic peak, etc., therefore, the embodiment of the present application first obtains the reference characteristic wavelength of each initial wavelength according to the distance between each initial wavelength and the characteristic wavelength, and then based on the difference between the initial wavelength and the reference characteristic wavelength, the wavelength which can more represent the tacrolimus drug component can be further screened, and the accuracy of the subsequent concentration detection is improved.

[0030] Preferably, in an embodiment of the present application, the method for obtaining the reference characteristic wavelength of each initial wavelength specifically comprises: taking any one initial wavelength as a target initial wavelength, taking the absolute value of the difference between the target initial wavelength and each characteristic wavelength as the distance parameter between the target initial wavelength and each characteristic wavelength, the smaller the distance parameter between the target initial wavelength and a certain characteristic wavelength, the closer the distance between the two, and the greater the reference value of the characteristic wavelength to the target initial wavelength, therefore, the characteristic wavelength corresponding to the minimum distance parameter can be taken as the reference characteristic wavelength of the target initial wavelength.

[0031] The reference characteristic wavelength of each initial wavelength can be obtained by the same method.

[0032] The smaller the difference between the initial wavelength and the corresponding reference characteristic wavelength, and the greater the reflection light intensity of the drug solution spectrum data and the waste liquid spectrum data at the initial wavelength, the more likely the initial wavelength is to represent the heparin drug component wavelength rather than the impurity component wavelength. Therefore, the effective degree of each initial wavelength can be obtained according to the difference between each initial wavelength and the reference characteristic wavelength, and the reflection light intensity of the drug solution spectrum data and the waste liquid spectrum data at the same initial wavelength. Subsequently, the to-be-analyzed wavelength representing the heparin drug component can be further screened based on the effective degree.

[0033] Preferably, in an embodiment of the present application, the method for obtaining the effective degree of each initial wavelength specifically comprises: performing negative correlation mapping on the distance parameter between the target initial wavelength and the reference characteristic wavelength to obtain a first effective coefficient of the target initial wavelength, and taking the average value of the reflection light intensity of the drug solution spectrum data and the waste liquid spectrum data at the target initial wavelength as a second effective coefficient of the target initial wavelength.

[0034] further integrating the first effective coefficient and the second effective coefficient and performing normalization processing, and limiting the calculation result in the range of 0 to 1, so as to obtain the effective degree of the target initial wavelength.

[0035] In an embodiment of the present application, the integration of the first effective coefficient and the second effective coefficient can be realized by calculating the sum or product value of the two, which is not limited herein.

[0036] As an example, in an embodiment of the present application, the expression of the effective degree of the target initial wavelength can be specifically as follows: wherein, represents the effective degree of the target initial wavelength; represents the distance parameter between the target initial wavelength and the corresponding reference characteristic wavelength; represents the first effective coefficient of the target initial wavelength; represents the reflection light intensity of the drug solution spectrum data at the target initial wavelength; represents the reflection light intensity of the waste liquid spectrum data at the target initial wavelength; represents the second effective coefficient of the target initial wavelength; represents a normalization function for normalization processing; represents a preset first adjustment parameter for preventing the denominator from being 0, the value range of in an embodiment of the present application, is set to 0.01, ​The specific value of the preset effective threshold can also be set by the implementer according to the specific implementation scene, which is not limited here.

[0037] It should be noted that in other embodiments of the present application, negative correlation mapping can also be achieved by other basic mathematical operations, which are not described here.

[0038] The effective degree of each initial wavelength can be obtained by the same method as described above. The greater the effective degree of a certain initial wavelength, the more likely it is that the initial wavelength represents the wavelength of the tacrolimus drug component in the drug solution spectrum data and the waste liquid spectrum data. Therefore, the to-be-analyzed wavelength can be selected from all initial wavelengths based on the effective degree.

[0039] Preferably, in an embodiment of the present application, the initial wavelength with an effective degree greater than a preset effective threshold can be used as the to-be-analyzed wavelength, wherein the preset effective threshold has a value range of 0.5 to 1. In an embodiment of the present application, the preset effective threshold is set to 0.8. The specific value of the preset effective threshold can also be set by the implementer according to the specific implementation scene, which is not limited here.

[0040] Step S2: obtaining a relative intensity coefficient of each to-be-analyzed wavelength in the waste liquid spectrum data according to the difference between the reflection intensity of each to-be-analyzed wavelength in the waste liquid spectrum data and the standard reflection intensity of the reference characteristic wavelength of each to-be-analyzed wavelength; and obtaining a regression weight of the waste liquid spectrum data at each to-be-analyzed wavelength according to the difference between the relative intensity coefficients of the to-be-analyzed wavelengths in the waste liquid spectrum data and the effective degree of each to-be-analyzed wavelength.

[0041] Compared with the drug solution sample, the waste liquid sample contains a large amount of impurities. The characteristic peaks formed by these impurities in the waste liquid spectrum data may overlap with the characteristic peaks of the tacrolimus drug, thereby masking the tacrolimus drug information in the waste liquid spectrum data and causing serious information interference. Therefore, if the reflection intensity of the to-be-analyzed wavelength in the waste liquid spectrum data is directly used for regression analysis in the subsequent process, the calculation result will be distorted. Therefore, in the embodiment of the present application, the relative intensity coefficient of each to-be-analyzed wavelength in the waste liquid spectrum data is first obtained according to the difference between the reflection intensity of each to-be-analyzed wavelength in the waste liquid spectrum data and the standard reflection intensity of the reference characteristic wavelength of each to-be-analyzed wavelength. Subsequently, the degree of interference on the waste liquid spectrum data at each to-be-analyzed wavelength can be accurately analyzed based on the difference between the relative intensity coefficients of the to-be-analyzed wavelengths in the waste liquid spectrum data, thereby improving the accuracy of the tacrolimus drug concentration detection.

[0042] Preferably, in an embodiment of the present application, the method for obtaining the relative intensity coefficient of each to-be-analyzed wavelength in the waste liquid spectrum data specifically comprises: The relative intensity coefficient of each analysis wavelength in the waste liquid spectrum data is obtained by taking the reflected light intensity of each analysis wavelength in the waste liquid spectrum data as the numerator and taking the standard reflected light intensity of the reference characteristic wavelength of each analysis wavelength as the denominator.

[0043] As an example, in one embodiment of the present application, the expression of the relative intensity coefficient of each analysis wavelength in the waste liquid spectrum data can be specifically as follows: wherein, represents the relative intensity coefficient of the i-th analysis wavelength in the waste liquid spectrum data; represents the reflected light intensity of the i-th analysis wavelength in the waste liquid spectrum data; represents the reflected light intensity of the i-th analysis wavelength in the waste liquid spectrum data; represents the standard reflected light intensity of the reference characteristic wavelength of the i-th analysis wavelength. The smaller the difference between the relative intensity coefficient of a certain analysis wavelength and other analysis wavelengths in the waste liquid spectrum data, the smaller the interference degree of the waste liquid spectrum data at the analysis wavelength, and the greater the reference value of the reflected light intensity of the analysis wavelength in the subsequent regression analysis, and the greater the effective degree of the analysis wavelength, and the greater the reference value of the reflected light intensity of the analysis wavelength in the waste liquid spectrum data. Therefore, the regression weight of each analysis wavelength in the waste liquid spectrum data can be obtained according to the difference between the relative intensity coefficient of each analysis wavelength in the waste liquid spectrum data and the effective degree of each analysis wavelength.

[0044] Preferably, in one embodiment of the present application, the method for obtaining the regression weight of each analysis wavelength in the waste liquid spectrum data specifically comprises: taking any one analysis wavelength as a target analysis wavelength, and obtaining a stability coefficient of the target analysis wavelength in the waste liquid spectrum data according to the difference between the relative intensity coefficient of the target analysis wavelength and each other analysis wavelength except the target analysis wavelength in the waste liquid spectrum data, wherein the greater the stability coefficient, the smaller the interference degree of the waste liquid spectrum data at the target analysis wavelength.

[0045] Preferably, in one embodiment of the present application, the method for obtaining the stability coefficient of the target analysis wavelength in the waste liquid spectrum data specifically comprises:

[0046] Preferably, in one embodiment of the present application, the method for obtaining the stability coefficient of the target analysis wavelength in the waste liquid spectrum data specifically comprises: ​First, the absolute value of the difference in the relative intensity coefficient between the target wavelength to be analyzed and each other wavelength to be analyzed except the target wavelength to be analyzed in the waste liquid spectral data is used as the relative intensity difference value between the target wavelength to be analyzed and each other wavelength to be analyzed in the waste liquid spectral data. The cumulative value of the relative intensity difference values ​​between the target wavelength to be analyzed and all other wavelengths to be analyzed in the waste liquid spectral data is negatively correlated with the accumulated value to obtain the stability coefficient of the waste liquid spectral data at the target wavelength to be analyzed.

[0047] As an example, in one embodiment of the present invention, the expression for the stability coefficient of the waste liquid spectrum data at the target wavelength to be analyzed can be specifically, for example, as follows: in, Indicates the stability coefficient of waste liquid spectrum data at the target wavelength to be analyzed; Represents the relative intensity coefficient of the target wavelength to be analyzed in the waste liquid spectrum data; Indicates the wavelengths other than the target wavelength in the waste liquid spectrum data. The relative intensity coefficients of other wavelengths to be analyzed; Indicates the target wavelength to be analyzed and the The relative intensity difference between other wavelengths to be analyzed; The value range is In one embodiment of the present invention, Set to 0.01, The specific value of can also be set by the implementer according to the specific implementation scenario and is not limited here. M represents the total number of wavelengths to be analyzed except the target wavelength to be analyzed.

[0048] It should be noted that in other embodiments of the present invention, negative correlation mapping may be achieved through other basic mathematical operations, which will not be described in detail here.

[0049] Then, the stability coefficient of the waste liquid spectral data at the target wavelength to be analyzed and the effectiveness of the target wavelength to be analyzed are integrated and normalized to obtain the regression weight of the waste liquid spectral data at the target wavelength to be analyzed, wherein the cumulative value of the regression weight of the waste liquid spectral data at all wavelengths to be analyzed is equal to 1.

[0050] In an embodiment of the present invention, the integration of the two can be achieved by calculating the sum or product of the stability coefficient of the waste liquid spectrum data at the target wavelength to be analyzed and the effectiveness of the target wavelength to be analyzed, which is not limited here.

[0051] As an example, in one embodiment of the present invention, the regression weight expression of the waste liquid spectrum data at the target wavelength to be analyzed can be specifically, for example, as follows: in, Represents the regression weight of the waste liquid spectrum data at the target wavelength to be analyzed; Indicates the stability coefficient of waste liquid spectrum data at the target wavelength to be analyzed; Indicates the effectiveness of the target wavelength to be analyzed; Indicates that the waste liquid spectrum data is The stability factor of the wavelength to be analyzed; Indicates the The effectiveness of the wavelength to be analyzed; Indicates the number of all wavelengths to be analyzed.

[0052] in, Used for Normalization processing is performed so that the cumulative value of the regression weights of the waste liquid spectrum data at all wavelengths to be analyzed is equal to 1.

[0053] The regression weight of the waste liquid spectrum data at each wavelength to be analyzed can be obtained by the same method as above.

[0054] Step S3: Based on the regression weight of the waste liquid spectrum data at each wavelength to be analyzed, a weighted regression analysis is performed on the reflected light intensity of the drug solution spectrum data and the waste liquid spectrum data at each wavelength to be analyzed to obtain the tacrolimus drug concentration in the blood sample solution.

[0055] Through the above process, the regression weight of the waste liquid spectral data at each wavelength to be analyzed is obtained. The greater the regression weight of the waste liquid spectral data at a certain wavelength to be analyzed, the greater the reference value of the reflected light intensity of the waste liquid spectral data at the wavelength to be analyzed in the regression analysis. At the same time, since the impurity content in the drug solution sample is relatively low, the drug solution spectral data is weakly interfered by the impurities, and therefore the reflected light intensity of the drug solution spectral data at each wavelength to be analyzed can be directly used for regression analysis. Therefore, based on the regression weight of the waste liquid spectral data at each wavelength to be analyzed, the reflected light intensity of the drug solution spectral data and the waste liquid spectral data at each wavelength to be analyzed can be weighted regression analysis to obtain the tacrolimus drug concentration in the blood sample solution, thereby improving the accuracy of the tacrolimus drug concentration detection in the blood sample solution.

[0056] Preferably, in one embodiment of the present invention, the method for obtaining the tacrolimus drug concentration in the blood sample solution specifically includes: Since the interference of the drug solution spectrum data at each wavelength to be analyzed is relatively weak, the regression weight of the drug solution spectrum data at each wavelength to be analyzed can be regarded as a numerical value 1. Therefore, the reflected light intensity of the drug solution spectrum data at each wavelength to be analyzed, and the product value of the reflected light intensity of the waste liquid spectrum data at each wavelength to be analyzed and the regression weight are input into the weighted regression model. The tacrolimus drug concentration in the blood sample solution is output through the weighted regression model. The weighted regression model can be obtained through the spectrum data of the tacrolimus drug solution with a known concentration, and will not be described here.

[0057] It should be noted that the above-mentioned embodiment sequence of the present application is only for description, and does not represent the advantages and disadvantages of the embodiments. The processes depicted in the drawings do not necessarily require the specific order or continuous order shown to achieve the desired results. In some embodiments, multi-task processing and parallel processing are also possible or can be advantageous.

[0058] Each embodiment in the specification is described in a progressive manner, and the same or similar parts between each embodiment can be referred to each other. Each embodiment focuses on the difference from other embodiments.

Claims

1. A tacrolimus drug concentration rapid detection device based on a microfluidic chip, characterized in that: The detection device includes a blood sampling area, a separation area, a drug solution storage area, a waste liquid storage area, and a spectrometer. The separation area is used to separate the tacrolimus drug in the blood sample solution and obtain a drug solution sample and a waste liquid sample. The spectrometer is used to collect drug solution spectral data of the drug solution sample in the drug solution storage area and waste liquid spectral data of the waste liquid sample in the waste liquid storage area, and detect the tacrolimus drug concentration in the blood sample solution based on the drug solution spectral data and the waste liquid spectral data. The method for detecting the tacrolimus drug concentration in the blood sample solution includes: Screening an initial wavelength based on the difference in reflected light intensity at the same wavelength between the drug solution spectral data and the waste liquid spectral data; obtaining standard reflected light intensities of multiple characteristic wavelengths from a standard spectrum of tacrolimus drug components, and obtaining a reference characteristic wavelength for each initial wavelength based on the distance between each initial wavelength and the characteristic wavelength; obtaining a validity level for each initial wavelength based on the difference between each initial wavelength and the reference characteristic wavelength, and the reflected light intensities of the drug solution spectral data and the waste liquid spectral data at the same initial wavelength; and screening a wavelength to be analyzed from all initial wavelengths based on the validity level; Obtaining a relative intensity coefficient for each wavelength to be analyzed in the waste liquid spectral data based on a difference between the reflected light intensity of the waste liquid spectral data at each wavelength to be analyzed and the standard reflected light intensity of a reference characteristic wavelength for each wavelength to be analyzed; obtaining a regression weight for the waste liquid spectral data at each wavelength to be analyzed based on the difference in the relative intensity coefficients between the wavelengths to be analyzed in the waste liquid spectral data and the effectiveness of each wavelength to be analyzed; Based on the regression weight of the waste liquid spectral data at each wavelength to be analyzed, a weighted regression analysis is performed on the reflected light intensity of the drug solution spectral data and the waste liquid spectral data at each wavelength to be analyzed to obtain the tacrolimus drug concentration in the blood sample solution.

2. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 1, characterized in that: The screening of the initial wavelength comprises: Normalizing the absolute value of the difference in reflected light intensity at the same wavelength between the liquid medicine spectrum data and the waste liquid spectrum data to obtain a reflected light intensity difference value at each wavelength between the liquid medicine spectrum data and the waste liquid spectrum data; The wavelength at which the reflected light intensity difference value is greater than a preset difference threshold is used as the initial wavelength.

3. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 1, characterized in that: The step of obtaining a reference characteristic wavelength for each initial wavelength comprises: Taking any initial wavelength as the target initial wavelength, and taking the absolute value of the difference between the target initial wavelength and each characteristic wavelength as the distance parameter between the target initial wavelength and each characteristic wavelength; The characteristic wavelength corresponding to the minimum value of the distance parameter is used as the reference characteristic wavelength of the target initial wavelength.

4. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 3, characterized in that: The effectiveness of obtaining each initial wavelength includes: Performing negative correlation mapping on the distance parameter between the target initial wavelength and the reference characteristic wavelength to obtain a first effective coefficient of the target initial wavelength; The average value of the reflected light intensity of the liquid medicine spectrum data and the waste liquid spectrum data at the target initial wavelength is used as the second effective coefficient of the target initial wavelength; The first effective coefficient and the second effective coefficient are integrated and normalized to obtain the effectiveness of the target initial wavelength.

5. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 1, characterized in that: The step of screening out the wavelength to be analyzed from all the initial wavelengths comprises: The initial wavelength whose effectiveness is greater than the preset effectiveness threshold is used as the wavelength to be analyzed.

6. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 1, characterized in that: The step of obtaining the relative intensity coefficient of each wavelength to be analyzed in the waste liquid spectrum data includes: The reflected light intensity of the waste liquid spectrum data at each wavelength to be analyzed is used as the numerator, the standard reflected light intensity of the reference characteristic wavelength of each wavelength to be analyzed is used as the denominator, and the ratio is used as the relative intensity coefficient of each wavelength to be analyzed in the waste liquid spectrum data.

7. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 1, characterized in that: The step of obtaining the regression weight of the waste liquid spectrum data at each wavelength to be analyzed includes: Taking any wavelength to be analyzed as a target wavelength to be analyzed, and obtaining a stability coefficient of the waste liquid spectrum data at the target wavelength to be analyzed based on a difference in the relative intensity coefficient between the target wavelength to be analyzed and each other wavelength to be analyzed except the target wavelength to be analyzed in the waste liquid spectrum data; The stability coefficient of the waste liquid spectral data at the target wavelength to be analyzed and the effectiveness of the target wavelength to be analyzed are integrated and normalized to obtain the regression weight of the waste liquid spectral data at the target wavelength to be analyzed, wherein the cumulative value of the regression weight of the waste liquid spectral data at all wavelengths to be analyzed is equal to a value of 1.

8. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 7, characterized in that: The stability coefficient of the waste liquid spectrum data obtained at the target wavelength to be analyzed includes: The absolute value of the difference between the target wavelength to be analyzed and each other wavelength to be analyzed except the target wavelength to be analyzed in the waste liquid spectrum data is used as the relative intensity difference value between the target wavelength to be analyzed and each other wavelength to be analyzed in the waste liquid spectrum data; Negative correlation mapping is performed on the accumulated values ​​of the relative intensity difference values ​​between the target wavelength to be analyzed and all other wavelengths to be analyzed in the waste liquid spectrum data to obtain a stability coefficient of the waste liquid spectrum data at the target wavelength to be analyzed.

9. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 1, characterized in that: The obtaining of the tacrolimus drug concentration in the blood sample solution comprises: The reflected light intensity of the drug solution spectral data at each wavelength to be analyzed, and the product value of the reflected light intensity of the waste liquid spectral data at each wavelength to be analyzed and the regression weight are input into the weighted regression model, and the tacrolimus drug concentration in the blood sample solution is output through the weighted regression model.

10. The device for rapid detection of tacrolimus drug concentration based on a microfluidic chip according to claim 1, characterized in that: The detection device further comprises a hydromagnet and a red blood cell wall breaking area. The hydromagnet is used to separate red blood cells in a blood sample solution, and the red blood cell wall breaking area is used to break the red blood cells separated by the hydromagnet.

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