WO2022160499A1 - Anomaly recognition method and anomaly recognition apparatus for specific protein response curve - Google Patents

Anomaly recognition method and anomaly recognition apparatus for specific protein response curve Download PDF

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Publication number
WO2022160499A1
WO2022160499A1 PCT/CN2021/092453 CN2021092453W WO2022160499A1 WO 2022160499 A1 WO2022160499 A1 WO 2022160499A1 CN 2021092453 W CN2021092453 W CN 2021092453W WO 2022160499 A1 WO2022160499 A1 WO 2022160499A1
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specific protein
response curve
sample
protein response
tested
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PCT/CN2021/092453
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French (fr)
Chinese (zh)
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易勇
邹海涛
王兴红
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深圳市科曼医疗设备有限公司
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Publication of WO2022160499A1 publication Critical patent/WO2022160499A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/49Scattering, i.e. diffuse reflection within a body or fluid
    • G01N21/51Scattering, i.e. diffuse reflection within a body or fluid inside a container, e.g. in an ampoule

Definitions

  • the invention relates to the technical field of sample detection, in particular to an abnormality identification method and identification device of a specific protein response curve, and also to an abnormality identification method of a sampling curve.
  • C-reactive protein C-reactive protein
  • CRP C-reactive protein
  • CRP Crohn's disease
  • CRP detection There are various commonly used methods to detect CRP, including nephelometry, transmission turbidimetry, radioimmunoassay, chemiluminescence, ELISA and point-of-care CRP detection (POCT).
  • the clinical laboratory methods for the determination of CRP in serum are mainly immunoturbidimetry, including latex-enhanced turbidimetry (referred to as turbidimetry) and rate nephelometry (referred to as turbidimetry). These two methods are mainly For automated analysis systems, rate nephelometry is mostly used in closed detection systems in the field of immunodetection, and latex-enhanced turbidimetry is mostly used in open detection systems in the field of biochemical detection.
  • a curve of voltage versus time based on light signals can be obtained, which is also called a specific protein response curve (also called a sampling curve for other samples).
  • the quality (validity) of the specific protein response curve is not checked too much, because the current detection accuracy is not high, even if the specific protein response curve exists Jitter or bulging has less impact on the detection results.
  • those skilled in the art have not thought about identifying whether the sampling curve is abnormal or how to deal with it after determining the abnormal type.
  • the main technical problem to be solved by the present invention is to provide an abnormality identification method and identification device for a specific protein response curve that can effectively identify whether there is an abnormal specific protein response curve.
  • an embodiment provides a method for identifying abnormality of a specific protein response curve, comprising:
  • the specific protein response curve is abnormal, obtain the second derivative of the specific protein response curve of the sample to be tested, and determine the abnormal type according to the second derivative of the specific protein response curve;
  • an embodiment provides an abnormality identification method for a sampling curve, including:
  • sampling curve If the sampling curve is abnormal, obtain the second-order derivative of the sampling curve of the sample to be tested, and determine the abnormality type according to the second-order derivative of the sampling curve;
  • Exception alarm information associated with the exception type is output.
  • an abnormality identification device for a specific protein response curve comprising:
  • reaction vessel for containing the sample to be tested
  • a light source for providing laser light to the sample to be tested in the reaction vessel
  • an optical signal receiver used to collect the optical signal generated by the laser through the sample to be tested, and convert the optical signal into an electrical signal
  • a data processing device in signal connection with the optical signal receiver, for:
  • Exception alarm information associated with the exception type is output.
  • an embodiment provides a computer-readable storage medium, where a program is stored on the medium, and the program can be executed by a processor to implement the method of the first aspect or the second aspect.
  • whether there is an abnormality is identified by the first-order derivative of the specific protein response curve, and the type of abnormality is determined according to its second-order derivative, and then the abnormality alarm information associated with the abnormality type is output.
  • the whole process is efficient and fast, In this way, users can not only quickly know whether the curve can be used for subsequent calculations, but also instruct users to take corresponding countermeasures through alarm information.
  • FIG. 1 is a schematic diagram of the structural composition of an abnormality identification device for a specific protein response curve according to an embodiment
  • FIG. 2 is a schematic diagram of the structural composition of an abnormality identification device for a specific protein response curve according to another embodiment
  • FIG. 3 is a schematic diagram of a specific protein response curve obtained by nephelometry according to an embodiment
  • FIG. 4 is a schematic diagram of a specific protein response curve obtained by nephelometry in another embodiment
  • FIG. 5 is a schematic diagram of a specific protein response curve obtained by nephelometry according to another embodiment
  • FIG. 6 is a schematic diagram of a specific protein response curve obtained by a turbidimetric method according to an embodiment
  • FIG. 7 is a schematic diagram of a specific protein response curve obtained by a turbidimetric method according to another embodiment
  • FIG. 9 is a flowchart of a method for identifying abnormality of a specific protein response curve according to an embodiment
  • 10 is a schematic diagram of the detection result when the specific protein response curve of an embodiment is not abnormal
  • 11 is a schematic diagram of detection results when there is abnormal fluctuation in the specific protein response curve of an embodiment
  • FIG. 12 is a schematic diagram of the detection result when a specific protein channel is abnormal in the specific protein response curve of an embodiment.
  • connection and “connection” mentioned in this application, unless otherwise specified, include both direct and indirect connections (connections).
  • the inventor thought of first obtaining the calibration curve according to the sample concentration of a series of samples with known concentrations.
  • the calibration curve is the corresponding relationship between the sample concentration and the curve characteristics of the sample.
  • it is necessary to detect the concentration of the sample to be tested first obtain the specific protein response curve of the sample, then obtain a curve feature of the specific protein response curve, and then substitute the curve feature into the calibration curve, the specific protein concentration of the sample can be obtained. .
  • the inventor found that whether there is abnormality (such as fluctuation or bulge) in the reaction curve will have a great impact on the detection results of the above method, so the inventor has carried out the present invention in the process of conceiving how to further improve the above detection method. create.
  • the principle of specific protein reaction detection is based on the reaction of antigens and antibodies in a specific electrolyte solution to rapidly form immune complex particles, causing turbidity in the reaction solution. also gradually increased.
  • the intensity of the optical signal received by the optical signal receiver 30 also increases with time.
  • turbidimetry the intensity of the optical signal received by the optical signal receiver 30 decreases over time.
  • C-reactive protein is a type of specific protein test.
  • FIG. 1 shows the detection process of nephelometric method, including a light source 20, a reaction vessel 10 and a light signal receiver 30, wherein the reaction vessel 10 is filled with a reaction liquid, the light source 20 is vertically injected into the reaction vessel 10, The microspheres in the reaction solution are irradiated through the wall of the reaction container 10, and scattered, and the scattered light enters the wall of the reaction container 10 from an angle other than 90 degrees (with the side wall of the reaction container 10), and then enters the air through the wall of the reaction container 10, and finally to the optical signal receiver 30.
  • the scattered light passes through three different media, namely, the reaction liquid, the reaction vessel 10 and air. Since the scattered light passes through the three media from a direction other than 90 degrees, the scattered light will be refracted during propagation.
  • FIG. 2 can represent the detection process of turbidimetry, including a light source 20 , a reaction vessel 10 and a light signal receiver 30 , wherein the reaction vessel 10 is filled with a reaction liquid, and the light source 20 is vertically injected into the reaction vessel 10 , passing through the reaction vessel 10 .
  • the microspheres in the reaction solution are irradiated through the wall of the reaction container 10 to transmit, and then enter the air through the wall of the reaction container 10 , and finally reach the optical signal receiver 30 .
  • this embodiment provides an abnormality identification device for a specific protein response curve, including a reaction vessel 10 , a light source 20 , an optical signal receiver 30 and a data processing device 50 .
  • the reaction container 10 is used for containing the sample to be tested, and can be, for example, a transparent reaction container 10 .
  • the light source 20 is used as the light source 20 used in the nephelometric method, and is used for providing laser light to the sample to be measured in the reaction vessel 10 .
  • the optical signal receiver 30 is disposed on the optical path of the scattered light formed by the laser light through the sample to be tested, and is used for collecting the scattered light and converting the optical signal of the scattered light into an electrical signal.
  • the data processing device 50 is signally connected to the optical signal receiver 30, which is used to obtain the specific protein response curve of the sample to be tested according to the electrical signal.
  • the specific protein response curve shown in FIG. Monotonic changes in the concentration of a specific protein.
  • the formula of the specific protein response curve of the sample to be tested including:
  • Va F( ta ).
  • the preset threshold is zero. If minF'(t a ) is greater than or equal to zero, it means that the specific protein response curve of the sample to be tested is an increasing function, and there is no abnormality in the specific protein response curve of the sample to be tested. '(t a ) is less than zero, the specific protein response curve of the sample to be tested is abnormal.
  • the second derivative of the specific protein response curve of the sample to be tested is also obtained.
  • the derivative determines the effective sampling time in the total sampling time, and then determines the abnormality type according to the length of the effective sampling time.
  • the data processing device 50 obtains the second derivative F'' (t a ) of the specific protein response curve of the sample to be tested, The effective time of sampling is determined according to the second derivative.
  • the specific protein response curve of the sample to be tested within the effective time of sampling needs to satisfy that F”(t a ) is less than zero.
  • t 1 is the start time point of the effective sampling time
  • t 2 is the end time point of the effective sampling time.
  • the sampling valid time can also be selected according to other rules.
  • the data processing device 50 determines the abnormality type according to the length of the effective sampling time.
  • the first type is that the specific protein response curve has abnormal fluctuations, which means that the specific protein response curve is not strictly monotonically increasing, but there are still curve parts that can be used for subsequent calculations.
  • the class is an abnormality of a specific protein channel, which means that the specific protein curve obtained this time has a serious deviation and is invalid.
  • the specific judgment criteria may be: the data processing device 50 obtains the ratio of the sampling effective time to the total sampling time, and compares the ratio with the preset threshold P, if the sampling effective time is greater than the preset threshold P, then the specific protein response curve fluctuates Abnormal, if the effective sampling time is less than the preset threshold P, the specific protein response curve has an abnormal specific protein channel.
  • the value of P can be from 40% to 60%, taking 50% as an example, when the ratio of the effective sampling time to the total sampling time exceeds 50%, that is, the specific protein reaction is continuously half of the total sampling time. There is no abnormality in the curve, and it is determined that the curve is still partially available.
  • the data processing device 50 After the abnormality type is determined, the data processing device 50 will output alarm information associated with the abnormality type. For example, when there is an abnormal fluctuation in the specific protein response curve, the text message "There is a fluctuation abnormality in the specific protein response curve" is output. When the channel is abnormal, the text message "Specific protein channel is abnormal” is output. In addition, when there is an abnormal fluctuation in the specific protein response curve, the data processing device 50 can calculate the specific protein concentration of the sample to be tested according to the specific protein response curve within the sampling valid time, and if the specific protein channel is abnormal, the data processing device 50 does not The specific protein response curve is calculated, or the detection results obtained from the curve are masked before.
  • the abnormal response curve can be effectively identified by the above abnormality identification device, and different alarm information can be output according to different types of the abnormality, and different processing steps can be taken subsequently, which is more pertinent and practical.
  • the specific protein concentration of the sample to be tested can be calculated according to the specific protein response curve.
  • the calculation method is described below.
  • the abnormal The identification device processes the data to obtain the specific protein response concentration of the sample to be tested.
  • the obtained specific protein response curve can also be output to the concentration calculation device, and the concentration calculation device obtains the result.
  • the abnormality identification device further includes a storage device 40, which is used for storing the specific protein concentration of each known concentration sample and the corresponding specific protein response curve obtained based on the nephelometric method.
  • the number of known concentration samples is N, that is, there are N known concentration samples B 1 , B 2 , . . . , B i , .
  • the specific protein concentration of the sample with known concentration is C i , and 0 ⁇ C 1 ⁇ C 2 ⁇ ... ⁇ C i ⁇ ... ⁇ C N , 1 ⁇ i ⁇ N.
  • V bi Fi (t b ).
  • t b is the sampling time of the known concentration sample
  • V bi is the voltage obtained when the ith known concentration sample is sampled
  • T b is the known concentration sample The end time point of the total sampling time.
  • the specific protein response curve of any sample with a known concentration it is also determined whether the specific protein response curve of the known concentration sample is abnormal, and if there is an abnormality, the known concentration of the abnormal specific protein response curve is determined. The sample is re-tested to obtain the corresponding specific protein response curve again, until the specific protein response curve of each known concentration sample has no abnormality.
  • the way of judging whether the specific protein response curve of the i-th known concentration sample is abnormal can be: obtaining the first derivative F i of the specific protein response curve of the i-th known concentration sample , (t b ), Then obtain the minimum value minFi '(t b ) of the first derivative Fi '(t b ), if minFi '(t b ) is not less than zero, the specific protein response curve of the ith known concentration sample does not exist Otherwise, the specific protein response curve of the ith known concentration sample is abnormal, then the known concentration sample is detected again until the first derivative of the specific protein response curve of the known concentration sample is not less than 0.
  • the extraction time period is the time period used to extract curve features. . After acquiring the extraction time period, the data processing device 50 extracts the curve characteristics corresponding to the specific protein response curve of the sample to be tested in the extraction time period.
  • the calculation formula of the voltage difference D a1 includes:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • T a is the end time point of the total sampling time
  • the voltage difference D a1 is used as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the area S a1 between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested is calculated, and the calculation formula of the area S a1 include:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • T a is the end time point of the total sampling time.
  • a1 is used as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the specific protein response curve of the sample to be tested has abnormal fluctuations, and the specific protein response curve of the sample to be extracted is extracted at the extraction time.
  • Curve features corresponding to the segment including:
  • the calculation formula of the voltage difference D a2 includes:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • t 1 is the start time point of the effective sampling time
  • t 2 is the end time point of the effective time of sampling
  • the voltage difference D a2 is taken as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the calculation formula of the area S a2 includes:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • t 1 is the start time point of the effective sampling time
  • t 2 is the end time point of the effective time of sampling
  • the area S a2 is taken as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the curve characteristics r 1 , r 2 , . ,...,r N , 1 ⁇ i ⁇ N, r i is the curve characteristic corresponding to the specific protein response curve of the i-th known concentration sample in the extraction time period.
  • t b1 and t b2 are the sampling times of two points on the specific protein response curve of the i-th sample with known concentration, 0 ⁇ t b1 ⁇ t b2 ⁇ T b , D bi is the voltage difference, and T b is the known concentration
  • D a1 or D a2 the curve characteristic of the sample to be tested
  • t b2 t a2
  • t b1 t a1
  • take the voltage difference Dbi as the i-th known concentration
  • the curve characteristic ri of the specific protein response curve of the sample is the curve characteristic of the specific protein response curve of the sample.
  • the area between two different points on the specific protein response curve of the known concentration sample is calculated to obtain the area S bi , and the calculation formula of the area S bi includes:
  • S bi is the area between two different points on the specific protein response curve of the sample with known concentration
  • t b1 and t b2 are the sampling time of two points on the specific protein response curve of the sample with known concentration
  • T b is the end time point of the total sampling time of the sample with known concentration
  • the data processing device 50 After obtaining the curve characteristics of the specific protein response curve of the sample to be tested, the data processing device 50 inputs the curve characteristics of the sample to be tested into the calibration function relationship, so as to obtain a specific protein concentration, which is used as the specific protein concentration of the sample to be tested. specific protein concentration.
  • this embodiment provides an abnormality identification device for a specific protein response curve, including a reaction vessel 10 , a light source 20 , an optical signal receiver 30 and a data processing device 50 .
  • the reaction container 10 is used for containing the sample to be tested, and can be, for example, a transparent reaction container 10 .
  • the light source 20 is used as the light source 20 used in the nephelometric method, and is used for providing laser light to the sample to be tested in the reaction vessel 10 .
  • the optical signal receiver 30 is disposed on the optical path of the transmitted light formed by the laser through the sample to be tested, and is used for collecting the transmitted light and converting the optical signal of the transmitted light into an electrical signal.
  • the data processing device 50 is signally connected to the optical signal receiver 30, which is used to obtain the specific protein response curve of the sample to be tested according to the electrical signal.
  • the specific protein response curve shown in FIG. Monotonic changes in the concentration of a specific protein.
  • the formula of the specific protein response curve of the sample to be tested including:
  • Va F( ta ).
  • the curve may be smoothed (for example, mean smoothing or median smoothing), so as to obtain a smoother response curve, which is helpful for subsequent calculation (feature extraction of the curve).
  • the preset threshold is zero. If max(F'(t a )) is less than or equal to zero, it means that the specific protein response curve of the sample to be tested is a decreasing function, and the specific protein response curve of the sample to be tested is not abnormal. , if max(F'(t a )) is greater than zero, the specific protein response curve of the sample to be tested is abnormal.
  • the second derivative of the specific protein response curve of the sample to be tested is also obtained.
  • the derivative determines the effective sampling time in the total sampling time, and then determines the abnormality type according to the length of the effective sampling time.
  • the data processing device 50 obtains the second derivative F'' (t a ) of the specific protein response curve of the sample to be tested, The effective time of sampling is determined according to the second derivative.
  • the specific protein response curve of the sample to be tested within the effective time of sampling needs to satisfy that F”(t a ) is greater than zero.
  • t 1 is the start time point of the effective sampling time
  • t 2 is the end time point of the effective sampling time.
  • Fig. 7 where the arrow points to the specific protein response curve is the fluctuation
  • the data processing device 50 determines the abnormality type according to the length of the effective sampling time.
  • the first type is that the specific protein response curve has abnormal fluctuations, which means that the specific protein response curve is not strictly monotonically decreasing, but there are still curve parts that can be used for subsequent calculations.
  • the class is an abnormality of a specific protein channel, which means that the specific protein curve obtained this time has a serious deviation and is invalid.
  • the specific judgment criteria can be:
  • the specific judgment criteria may be: the data processing device 50 obtains the ratio of the sampling effective time to the total sampling time, and compares the ratio with the preset threshold P, if the sampling effective time is greater than the preset threshold P, then the specific protein response curve fluctuates Abnormal, if the effective sampling time is less than the preset threshold P, the specific protein response curve has an abnormal specific protein channel.
  • the value of P can be from 40% to 60%, taking 50% as an example, when the ratio of the effective sampling time to the total sampling time exceeds 50%, that is, the specific protein reaction is continuously half of the total sampling time. There is no abnormality in the curve, and it is determined that the curve is still partially available.
  • the data processing device 50 After the abnormality type is determined, the data processing device 50 will output alarm information associated with the abnormality type. For example, when there is an abnormal fluctuation in the specific protein response curve, the text message "There is a fluctuation abnormality in the specific protein response curve" is output. When the channel is abnormal, the text message "Specific protein channel is abnormal” is output. In addition, when there is an abnormal fluctuation in the specific protein response curve, the data processing device 50 can calculate the specific protein concentration of the sample to be tested according to the specific protein response curve within the sampling valid time, and if the specific protein channel is abnormal, the data processing device 50 does not The specific protein response curve is calculated, or the detection results obtained from the curve are masked before.
  • the abnormal response curve can be effectively identified by the above abnormality identification device, and different alarm information can be output according to different types of the abnormality, and different processing steps can be taken subsequently, which is more pertinent and practical.
  • the specific protein concentration of the sample to be tested can be calculated according to the specific protein response curve.
  • the calculation method is described below.
  • the abnormal The identification device processes the data to obtain the specific protein response concentration of the sample to be tested.
  • the obtained specific protein response curve can also be output to the concentration calculation device, and the concentration calculation device obtains the result.
  • the abnormality identification device further includes a storage device 40, which is used for storing the specific protein concentration of each known concentration sample and the corresponding specific protein response curve obtained based on the turbidimetric method.
  • the number of known concentration samples is N, that is, there are N known concentration samples B 1 , B 2 , . . . , B i , .
  • the specific protein concentration of the sample with known concentration is C i , and 0 ⁇ C 1 ⁇ C 2 ⁇ ... ⁇ C i ⁇ ... ⁇ C N , 1 ⁇ i ⁇ N.
  • V bi Fi (t b ).
  • the extraction time period is the time period used to extract curve features. . After acquiring the extraction time period, the data processing device 50 extracts the curve characteristics corresponding to the specific protein response curve of the sample to be tested in the extraction time period.
  • includes:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • T a is the end time point of the total sampling time
  • is used as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the area S a1 between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested is calculated, and the calculation formula of the area S a1 include:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • T a is the end time point of the total sampling time.
  • a1 is used as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the specific protein response curve of the sample to be tested has abnormal fluctuations, and the specific protein response curve of the sample to be extracted is extracted at the extraction time.
  • Curve features corresponding to the segment including:
  • includes:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • t 1 is the start time point of the effective sampling time
  • t 2 is the end time point of the effective sampling time
  • is used as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the calculation formula of the area S a2 includes:
  • t a1 is the start time point of the extraction time period
  • t a2 is the end time point of the extraction time period
  • t 1 is the start time point of the effective sampling time
  • t 2 is the end time point of the effective time of sampling
  • the area S a2 is taken as the curve characteristic of the specific protein response curve of the sample to be tested.
  • the absolute value of the voltage difference between two different points on the specific protein response curve of the known concentration sample is calculated to obtain the absolute value of the voltage difference
  • includes:
  • t b1 and t b2 are the sampling times of two points on the specific protein response curve of the ith known concentration sample, 0 ⁇ t b1 ⁇ t b2 ⁇ T b ,
  • is the absolute value of the voltage difference
  • T b is the end time point of the total sampling time of the sample with known concentration. If the curve characteristic of the sample to be tested is
  • the area between two different points on the specific protein response curve of the known concentration sample is calculated to obtain the area S bi , and the calculation formula of the area S bi includes:
  • the data processing device 50 After obtaining the curve characteristics of the specific protein response curve of the sample to be tested, the data processing device 50 inputs the curve characteristics of the sample to be tested into the calibration function relationship, so as to obtain a specific protein concentration, which is used as the specific protein concentration of the sample to be tested. specific protein concentration.
  • This embodiment provides an abnormal identification method for a specific protein response curve, as shown in Figure 9, including steps:
  • Step 100 Perform specific protein detection on the sample to be tested within a preset total sampling time to obtain a specific protein response curve of the sample to be tested.
  • the specific protein response curve of the sample to be tested is a monotonic function over the total sampling time.
  • the detection methods include specific protein detection of the sample to be tested within a preset total sampling time based on nephelometric method and specific protein detection of the sample to be tested based on nephelometric method within a preset total sampling time.
  • the turbidimetric method is used to detect the specific protein of the sample to be tested, and the obtained curve is an increasing function as shown in Figure 3. If the specific protein detection of the sample to be tested is performed based on the transmission turbidimetric method, the obtained curve is a decreasing function as shown in Figure 6.
  • the two detection methods can express a specific protein response curve using the same formula, which is:
  • Va F( ta ).
  • ta is the sampling time of the sample to be tested
  • Va is the voltage obtained during sampling
  • T a is the end time point of the total sampling time.
  • Step 200 Obtain the first derivative of the specific protein response curve of the sample to be tested.
  • Step 300 identify whether there is an abnormality in the specific protein response curve, if there is an abnormality, go to step 400 , and if there is no abnormality, go to step 600 .
  • the specific protein response curve of the sample to be tested is obtained based on the nephelometric method, and it is determined whether the minimum value minF '(ta) of the first derivative is less than zero. If it is less than zero, the specific protein response curve is abnormal.
  • the specific protein response curve of the sample to be tested is obtained based on the turbidimetric method, and it is determined whether the maximum value max(F'(t a )) of the first derivative is greater than zero, and if it is greater than zero, the specific protein response curve is determined. There is an exception.
  • Step 400 Obtain the second derivative of the specific protein response curve of the sample to be tested, and determine the abnormality type according to the second derivative of the specific protein response curve.
  • the second derivative of the specific protein response curve of the sample to be tested is also obtained.
  • the derivative determines the effective sampling time in the total sampling time, and then determines the abnormality type according to the length of the effective sampling time.
  • the second derivative F′′(t a ) of the specific protein response curve of the sample to be tested is obtained, and according to the second derivative Determine the sampling valid time.
  • the specific protein response curve of the sample to be tested is obtained based on the nephelometric method, and the specific protein response curve of the sample to be tested within the valid sampling period needs to satisfy that F′′(t a ) is less than zero, and 0 ⁇ t 1 ⁇ t 2 ⁇ T a , t 1 is the start time point of the effective sampling time, and t 2 is the end time point of the effective sampling time.
  • the specific protein response curve of the sample to be tested is obtained based on the turbidimetric method, and the specific protein response curve of the sample to be tested within the valid sampling period needs to satisfy that F′′(t a ) is greater than zero. Moreover, 0 ⁇ t 1 ⁇ t 2 ⁇ T a , t 1 is the start time point of the effective sampling time, and t 2 is the end time point of the effective sampling time.
  • sampling valid time can also be selected according to other rules.
  • the abnormality type is determined according to the length of the valid sampling time.
  • the first type is that the specific protein response curve has abnormal fluctuations, which means that the specific protein response curve is not strictly monotonically decreasing, but there are still curve parts that can be used for subsequent calculations.
  • the class is an abnormality of a specific protein channel, which means that the specific protein curve obtained this time has a serious deviation and is invalid.
  • the specific judgment criteria can be:
  • the specific judgment criteria may be: obtaining the ratio of the effective sampling time to the total sampling time, and comparing the ratio with the preset threshold P. If the sampling effective time is greater than the preset threshold P, the specific protein response curve has abnormal fluctuations. If the effective time is less than the preset threshold P, the specific protein response curve has abnormal specific protein channel.
  • the value of P can be from 40% to 60%, taking 50% as an example, when the ratio of the effective sampling time to the total sampling time exceeds 50%, that is, the specific protein reaction is continuously half of the total sampling time. There is no abnormality in the curve, and it is determined that the curve is still partially available.
  • Step 500 Output abnormal alarm information associated with the abnormal type.
  • the text information "There is an abnormal fluctuation in the response curve of a specific protein” is output, and when the specific protein channel is abnormal, the text information "Abnormality in the specific protein channel” is output.
  • the specific protein concentration of the sample to be tested can be calculated according to the specific protein response curve within the valid sampling period, and if the specific protein channel is abnormal, it is not calculated based on the specific protein response curve. Or mask the detection results obtained from the curve before.
  • the calculation method of obtaining the specific protein concentration of the sample to be tested can refer to the description in Example 1.
  • the specific protein concentration of the sample to be tested can be obtained.
  • the calculation method of the concentration can refer to the description of the second embodiment.
  • Step 600 End the abnormality identification process. End the abnormality identification process. If the specific protein response curve is obtained based on nephelometric method, the calculation method to obtain the specific protein concentration of the sample to be tested can refer to the description in Example 1. If the specific protein response curve is obtained based on the turbidimetric method, For the calculation method to obtain the specific protein concentration of the sample to be tested, refer to the description of the second embodiment.
  • the detection result interface is shown in Figure 10.
  • the detection result interface is shown in Figure 11
  • the detection result and alarm information will be displayed in the lower left corner at the same time.
  • the interface of the detection result is shown in Figure 12. Only the alarm information is displayed in the lower left corner of the interface and the detection result is shielded.
  • Embodiments 1 to 3 are all described by taking a specific protein as an example.
  • the sampling curve of the sample is a monotonic function
  • the abnormality identification can be implemented in a similar manner as in the above-mentioned embodiment.
  • the program can also be stored in a server, another computer, a magnetic disk, an optical disk, a flash disk or a mobile hard disk and other storage media, and saved by downloading or copying All or part of the functions in the above embodiments can be implemented when the program in the memory is executed by the processor.
  • whether there is an abnormality is identified by the first-order derivative of the specific protein response curve, and the type of abnormality is determined according to its second-order derivative, and then the abnormality alarm information associated with the abnormality type is output.
  • the whole process is efficient and fast, In this way, users can not only quickly know whether the curve can be used for subsequent calculations, but also instruct users to take corresponding countermeasures through alarm information.

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Abstract

Provided are an anomaly recognition method and anomaly recognition apparatus for a specific protein response curve. The anomaly recognition method comprises: performing, within a preset total sampling time, specific protein testing on a sample to be subjected to testing, so as to acquire a specific protein response curve of said sample (100), wherein the specific protein response curve of said sample is a monotonic function within the total sampling time; acquiring a first-order derivative of the specific protein response curve of said sample (200); according to the first-order derivative, recognizing whether the specific protein response curve is abnormal (300); if the specific protein response curve is abnormal, acquiring a second-order derivative of the specific protein response curve of said sample, and determining an anomaly type according to the second-order derivative of the specific protein response curve (400); and outputting anomaly alarm information associated with the anomaly type (500). By means of the anomaly recognition method, an anomaly and an anomaly type of a specific protein response curve can be effectively and pertinently recognized.

Description

特定蛋白反应曲线的异常识别方法及识别装置Abnormal identification method and identification device of specific protein response curve 技术领域technical field
本发明涉及样本检测技术领域,具体涉及一种特定蛋白反应曲线的异常识别方法及识别装置,还涉及一种采样曲线的异常识别方法。The invention relates to the technical field of sample detection, in particular to an abnormality identification method and identification device of a specific protein response curve, and also to an abnormality identification method of a sampling curve.
背景技术Background technique
特定蛋白,主要是检测血清中的特定功能性蛋白,不同的特定蛋白的结果数值可以判断出不同的疾病。以C反应蛋白(CRP)为例,C反应蛋白(CRP)是肝脏合成的一种急性炎症正时相反应蛋白,也是一种特定蛋白。正常人血中的CRP浓度很低,在机体突遇紧张、组织创伤和各种炎症刺激时合成快速增加,并从肝细胞中分泌入血液,在感染发生后12-18小时即可检测到高水平的CRP。在感染发生后的12-14天升高的CRP可降至基线水平。因此多年来—直是评价炎症性疾病的指标之一,并且升高幅度与感染的程度呈相关。CRP作为诊断细菌感染的重要标志物之一,已广泛应用于临床。CRP还是一个评估心脏病发生率、复发率、死亡率的临床重要指标。近年来的研究发现,炎症在动脉粥样硬化及肿瘤的发生、发展过程中起重要作用。鉴于血清CRP的重要作用,其测量的准确性受到了广泛的关注。Specific proteins are mainly used to detect specific functional proteins in serum. The results of different specific proteins can determine different diseases. Taking C-reactive protein (CRP) as an example, C-reactive protein (CRP) is a kind of acute inflammation positive phase response protein synthesized by the liver, and it is also a specific protein. The concentration of CRP in normal human blood is very low. When the body encounters sudden stress, tissue trauma and various inflammatory stimuli, its synthesis increases rapidly, and it is secreted into the blood from liver cells. High levels can be detected 12-18 hours after infection. level of CRP. Elevated CRP decreased to baseline levels 12-14 days after infection. Therefore, it has been one of the indicators for evaluating inflammatory diseases for many years, and the increase is related to the degree of infection. As one of the important markers for the diagnosis of bacterial infection, CRP has been widely used in clinical practice. CRP is also a clinically important index to evaluate the incidence, recurrence and mortality of heart disease. Recent studies have found that inflammation plays an important role in the occurrence and development of atherosclerosis and tumors. Given the important role of serum CRP, the accuracy of its measurement has received extensive attention.
检测CRP的常用方法多种多样,其中包括散射比浊法、透射比浊法,放射免疫测定、化学发光法、ELISA法及床旁CRP检测(POCT)等。目前临床实验室测定血清中CRP的方法主要是免疫浊度法,包括乳胶增强透射比浊法(简称透射比浊法)和速率散射比浊法(简称散射比浊法),这两种方法主要用于自动化分析***,速率散射比浊法多用于免疫检测领域的封闭检测***,乳胶增强透射比浊法多用于生化检测领域的开放检测***。运用透射比浊法和散射比浊法进行样本检测时,可以得到基于光信号得到的电压关于时间的变化曲线,该曲线也被称为特定蛋白反应曲线(其他样本时也可被称为采样曲线),目前根据该特定蛋白反应曲线得到样本浓度的方法中,并不会过多地对特定蛋白反应曲线的质量(有效性)进行检查,原因在于当前检测精度不高,即便特定蛋白反应曲线存在抖动或鼓包,对检测结果的影响也较小。目前本领域技术人员没有去想过识别采样曲线是否异常或是确定其异常类型后如何处理。There are various commonly used methods to detect CRP, including nephelometry, transmission turbidimetry, radioimmunoassay, chemiluminescence, ELISA and point-of-care CRP detection (POCT). At present, the clinical laboratory methods for the determination of CRP in serum are mainly immunoturbidimetry, including latex-enhanced turbidimetry (referred to as turbidimetry) and rate nephelometry (referred to as turbidimetry). These two methods are mainly For automated analysis systems, rate nephelometry is mostly used in closed detection systems in the field of immunodetection, and latex-enhanced turbidimetry is mostly used in open detection systems in the field of biochemical detection. When using nephelometry and nephelometry for sample detection, a curve of voltage versus time based on light signals can be obtained, which is also called a specific protein response curve (also called a sampling curve for other samples). ), in the current method for obtaining the sample concentration based on the specific protein response curve, the quality (validity) of the specific protein response curve is not checked too much, because the current detection accuracy is not high, even if the specific protein response curve exists Jitter or bulging has less impact on the detection results. At present, those skilled in the art have not thought about identifying whether the sampling curve is abnormal or how to deal with it after determining the abnormal type.
发明内容SUMMARY OF THE INVENTION
本发明主要解决的技术问题是提供一种能够有效识别出特定蛋白反应曲线 是否存在异常的特定蛋白反应曲线的异常识别方法以及识别装置。The main technical problem to be solved by the present invention is to provide an abnormality identification method and identification device for a specific protein response curve that can effectively identify whether there is an abnormal specific protein response curve.
根据第一方面,一种实施例中提供一种特定蛋白反应曲线的异常识别方法,包括:According to the first aspect, an embodiment provides a method for identifying abnormality of a specific protein response curve, comprising:
在预设的采样总时间内对待测样本进行特定蛋白检测,以获取待测样本的特定蛋白反应曲线,所述待测样本的特定蛋白反应曲线在所述采样总时间内为单调函数;Perform specific protein detection on the sample to be tested within a preset total sampling time to obtain a specific protein response curve of the sample to be tested, and the specific protein response curve of the sample to be tested is a monotonic function within the total sampling time;
获取所述待测样本的特定蛋白反应曲线的一阶导数;obtaining the first derivative of the specific protein response curve of the sample to be tested;
根据所述一阶导数识别所述特定蛋白反应曲线是否存在异常;Identifying whether the specific protein response curve is abnormal according to the first derivative;
如果所述特定蛋白反应曲线存在异常,获取所述待测样本的特定蛋白反应曲线的二阶导数,根据所述特定蛋白反应曲线的二阶导数确定异常类型;If the specific protein response curve is abnormal, obtain the second derivative of the specific protein response curve of the sample to be tested, and determine the abnormal type according to the second derivative of the specific protein response curve;
输出与所述异常类型关联的异常报警信息。Exception alarm information associated with the exception type is output.
根据第二方面,一种实施例中提供一种采样曲线的异常识别方法,包括:According to a second aspect, an embodiment provides an abnormality identification method for a sampling curve, including:
在预设的采样总时间内对待测样本进行检测,以获取待测样本的采样曲线,所述待测样本的采样曲线在所述采样总时间内为单调函数;Detect the sample to be tested within a preset total sampling time to obtain a sampling curve of the sample to be tested, and the sampling curve of the sample to be tested is a monotonic function within the total sampling time;
获取所述待测样本的采样曲线的一阶导数;obtaining the first derivative of the sampling curve of the sample to be tested;
根据所述一阶导数识别所述采样曲线是否存在异常;Identifying whether the sampling curve is abnormal according to the first-order derivative;
如果所述采样曲线存在异常,获取所述待测样本的采样曲线的二阶导数,根据所述采样曲线的二阶导数确定异常类型;If the sampling curve is abnormal, obtain the second-order derivative of the sampling curve of the sample to be tested, and determine the abnormality type according to the second-order derivative of the sampling curve;
输出与所述异常类型关联的异常报警信息。Exception alarm information associated with the exception type is output.
根据第三方面,一种实施例中提供一种特定蛋白反应曲线的异常识别装置包括:According to a third aspect, an embodiment provides an abnormality identification device for a specific protein response curve, comprising:
反应容器,用于容纳待测样本;a reaction vessel for containing the sample to be tested;
光源,用于向所述反应容器内的待测样本提供激光;a light source for providing laser light to the sample to be tested in the reaction vessel;
光信号接收器,用于采集激光经待测样本产生的光信号,并将所述光信号转换为电信号;an optical signal receiver, used to collect the optical signal generated by the laser through the sample to be tested, and convert the optical signal into an electrical signal;
数据处理装置,与所述光信号接收器信号连接,用于:A data processing device, in signal connection with the optical signal receiver, for:
根据所述电信号获取待测样本的特定蛋白反应曲线,所述待测样本的特定蛋白反应曲线用于表示采样总时间内得到的电压随特定蛋白浓度的单调变化;Obtain the specific protein response curve of the sample to be tested according to the electrical signal, and the specific protein response curve of the sample to be tested is used to represent the monotonic change of the voltage obtained in the total sampling time with the concentration of the specific protein;
获取所述待测样本的特定蛋白反应曲线的一阶导数;obtaining the first derivative of the specific protein response curve of the sample to be tested;
根据所述一阶导数识别所述特定蛋白反应曲线是否存在异常;Identifying whether the specific protein response curve is abnormal according to the first derivative;
如果所述特定蛋白反应曲线存在异常,获取所述待测样本的特定蛋白反应曲线的二阶导数,根据所述特定蛋白反应曲线的二阶导数确定异常类型;If the specific protein response curve is abnormal, obtain the second derivative of the specific protein response curve of the sample to be tested, and determine the abnormal type according to the second derivative of the specific protein response curve;
输出与所述异常类型关联的异常报警信息。Exception alarm information associated with the exception type is output.
根据第四方面,一种实施例提供一种计算机可读存储介质,所述介质上存储有程序,所述程序能够被处理器执行以实现第一方面或第二方面所述的方法。According to a fourth aspect, an embodiment provides a computer-readable storage medium, where a program is stored on the medium, and the program can be executed by a processor to implement the method of the first aspect or the second aspect.
上述实施例中,通过特定蛋白反应曲线的一阶导数识别出是否有异常,又根据其二阶导数确定出异常的类型,再输出与所述异常类型关联的异常报警信息,整个过程高效快速,从而让用户不但快速知晓曲线的是否可用于后续的计算,还通过报警信息指示用户采取相应的应对措施。In the above embodiment, whether there is an abnormality is identified by the first-order derivative of the specific protein response curve, and the type of abnormality is determined according to its second-order derivative, and then the abnormality alarm information associated with the abnormality type is output. The whole process is efficient and fast, In this way, users can not only quickly know whether the curve can be used for subsequent calculations, but also instruct users to take corresponding countermeasures through alarm information.
附图说明Description of drawings
图1为一种实施例的特定蛋白反应曲线的异常识别装置的结构组成示意图;1 is a schematic diagram of the structural composition of an abnormality identification device for a specific protein response curve according to an embodiment;
图2为另一种实施例的特定蛋白反应曲线的异常识别装置的结构组成示意图;2 is a schematic diagram of the structural composition of an abnormality identification device for a specific protein response curve according to another embodiment;
图3为一种实施例的散射比浊法得到的特定蛋白反应曲线的示意图;3 is a schematic diagram of a specific protein response curve obtained by nephelometry according to an embodiment;
图4为另一种实施例的散射比浊法得到的特定蛋白反应曲线的示意图;4 is a schematic diagram of a specific protein response curve obtained by nephelometry in another embodiment;
图5为又一种实施例的散射比浊法得到的特定蛋白反应曲线的示意图;5 is a schematic diagram of a specific protein response curve obtained by nephelometry according to another embodiment;
图6为一种实施例的透射比浊法得到的特定蛋白反应曲线的示意图;6 is a schematic diagram of a specific protein response curve obtained by a turbidimetric method according to an embodiment;
图7为另一种实施例的透射比浊法得到的特定蛋白反应曲线的示意图;7 is a schematic diagram of a specific protein response curve obtained by a turbidimetric method according to another embodiment;
图8为又一种实施例的透射比浊法得到的特定蛋白反应曲线的示意图;8 is a schematic diagram of a specific protein response curve obtained by turbidimetry according to another embodiment;
图9为一种实施例的特定蛋白反应曲线的异常识别方法的流程图;9 is a flowchart of a method for identifying abnormality of a specific protein response curve according to an embodiment;
图10为一种实施例的特定蛋白反应曲线不存在异常时的检测结果示意图;10 is a schematic diagram of the detection result when the specific protein response curve of an embodiment is not abnormal;
图11为一种实施例的特定蛋白反应曲线存在波动异常时的检测结果示意图;11 is a schematic diagram of detection results when there is abnormal fluctuation in the specific protein response curve of an embodiment;
图12为一种实施例的特定蛋白反应曲线存在特定蛋白通道异常时的检测结果示意图。FIG. 12 is a schematic diagram of the detection result when a specific protein channel is abnormal in the specific protein response curve of an embodiment.
具体实施方式Detailed ways
下面通过具体实施方式结合附图对本发明作进一步详细说明。其中不同实施方式中类似元件采用了相关联的类似的元件标号。在以下的实施方式中,很多细节描述是为了使得本申请能被更好的理解。然而,本领域技术人员可以毫不费力的认识到,其中部分特征在不同情况下是可以省略的,或者可以由其他元件、材料、方法所替代。在某些情况下,本申请相关的一些操作并没有在说明书中显示或者描述,这是为了避免本申请的核心部分被过多的描述所淹没,而对于本领域技术人员而言,详细描述这些相关操作并不是必要的,他们根据说明书中的描述以及本领域的一般技术知识即可完整了解相关操作。The present invention will be further described in detail below through specific embodiments in conjunction with the accompanying drawings. Wherein similar elements in different embodiments have used associated similar element numbers. In the following embodiments, many details are described so that the present application can be better understood. However, those skilled in the art will readily recognize that some of the features may be omitted under different circumstances, or may be replaced by other elements, materials, and methods. In some cases, some operations related to the present application are not shown or described in the specification, in order to avoid the core part of the present application from being overwhelmed by excessive description, and for those skilled in the art, these are described in detail. The relevant operations are not necessary, and they can fully understand the relevant operations according to the descriptions in the specification and general technical knowledge in the field.
另外,说明书中所描述的特点、操作或者特征可以以任意适当的方式结合形成各种实施方式。同时,方法描述中的各步骤或者动作也可以按照本领域技术人员所能显而易见的方式进行顺序调换或调整。因此,说明书和附图中的各种顺序只是为了清楚描述某一个实施例,并不意味着是必须的顺序,除非另有说明其中某个顺序是必须遵循的。Additionally, the features, acts, or characteristics described in the specification may be combined in any suitable manner to form various embodiments. At the same time, the steps or actions in the method description can also be exchanged or adjusted in order in a manner obvious to those skilled in the art. Therefore, the various sequences in the specification and drawings are only for the purpose of clearly describing a certain embodiment and are not meant to be a necessary order unless otherwise stated, a certain order must be followed.
本文中为部件所编序号本身,例如“第一”、“第二”等,仅用于区分所描述的对象,不具有任何顺序或技术含义。而本申请所说“连接”、“联接”,如无特别说明,均包括直接和间接连接(联接)。The serial numbers themselves, such as "first", "second", etc., for the components herein are only used to distinguish the described objects, and do not have any order or technical meaning. The "connection" and "connection" mentioned in this application, unless otherwise specified, include both direct and indirect connections (connections).
发明人在构思如何根据采样曲线计算得到样本浓度时,想到了首先根据一系列已知浓度样本的样本浓度获得定标曲线,定标曲线是关于样本浓度和该样本的曲线特征的对应关系,在需要检测待测样本的浓度时,首先得到该样本的特定蛋白反应曲线,然后求得特定蛋白反应曲线的一个曲线特征,接着将该曲线特征代入定标曲线,则可求出样本的特定蛋白浓度。When contemplating how to calculate the sample concentration according to the sampling curve, the inventor thought of first obtaining the calibration curve according to the sample concentration of a series of samples with known concentrations. The calibration curve is the corresponding relationship between the sample concentration and the curve characteristics of the sample. When it is necessary to detect the concentration of the sample to be tested, first obtain the specific protein response curve of the sample, then obtain a curve feature of the specific protein response curve, and then substitute the curve feature into the calibration curve, the specific protein concentration of the sample can be obtained. .
基于此,发明人发现了反应曲线是否存在异常(例如波动或鼓包)对于上述方法的检测结果会有很大的影响,故发明人在构思如何进一步完善上述检测方法的过程中,进行了本发明创造。Based on this, the inventor found that whether there is abnormality (such as fluctuation or bulge) in the reaction curve will have a great impact on the detection results of the above method, so the inventor has carried out the present invention in the process of conceiving how to further improve the above detection method. create.
特定蛋白反应检测原理是依据抗原、抗体在特定的电解质溶液中反应,快速形成免疫复合物微粒,使反应液出现浊度,随着时间的推移,复合物微粒聚合得就会越大,浊度也逐渐变大。在散射比浊法中,光信号接收器30接收到光信号的强度,也随时间的推移越来越大。在透射比浊法中,光信号接收器30接收到光信号的强度,随时间的推移越来越小。C反应蛋白是特定蛋白检测项目的一种。The principle of specific protein reaction detection is based on the reaction of antigens and antibodies in a specific electrolyte solution to rapidly form immune complex particles, causing turbidity in the reaction solution. also gradually increased. In the nephelometric method, the intensity of the optical signal received by the optical signal receiver 30 also increases with time. In turbidimetry, the intensity of the optical signal received by the optical signal receiver 30 decreases over time. C-reactive protein is a type of specific protein test.
请参考图1,其可表示散射比浊法的检测过程,包括光源20、反应容器10和光信号接收器30,其中,反应容器10中装有反应液,光源20垂直射入反应容器10,穿过反应容器10壁照射到反应液中的微球上,发生散射,散射光从非90度(与反应容器10侧壁)的角度进入反应容器10壁,再通过反应容器10壁进入空气,最后到光信号接收器30。整个过程散射光分别经过了反应液、反应容器10和空气三种不同的介质,因为散射光从非90度的方向经过这三种介质,所以散射光在传播过程中会发生折射。Please refer to FIG. 1, which shows the detection process of nephelometric method, including a light source 20, a reaction vessel 10 and a light signal receiver 30, wherein the reaction vessel 10 is filled with a reaction liquid, the light source 20 is vertically injected into the reaction vessel 10, The microspheres in the reaction solution are irradiated through the wall of the reaction container 10, and scattered, and the scattered light enters the wall of the reaction container 10 from an angle other than 90 degrees (with the side wall of the reaction container 10), and then enters the air through the wall of the reaction container 10, and finally to the optical signal receiver 30. During the whole process, the scattered light passes through three different media, namely, the reaction liquid, the reaction vessel 10 and air. Since the scattered light passes through the three media from a direction other than 90 degrees, the scattered light will be refracted during propagation.
请参照图2,其可表示透射比浊法的检测过程,包括光源20、反应容器10和光信号接收器30,其中,反应容器10中装有反应液,光源20垂直射入反应容器10,穿过反应容器10壁照射到反应液中的微球上,发生透射,再通过反应容器10壁进入空气,最后到光信号接收器30。Please refer to FIG. 2 , which can represent the detection process of turbidimetry, including a light source 20 , a reaction vessel 10 and a light signal receiver 30 , wherein the reaction vessel 10 is filled with a reaction liquid, and the light source 20 is vertically injected into the reaction vessel 10 , passing through the reaction vessel 10 . The microspheres in the reaction solution are irradiated through the wall of the reaction container 10 to transmit, and then enter the air through the wall of the reaction container 10 , and finally reach the optical signal receiver 30 .
实施例一Example 1
请参照图1,本实施例中提供了一种特定蛋白反应曲线的异常识别装置,包括反应容器10、光源20、光信号接收器30和数据处理装置50。Referring to FIG. 1 , this embodiment provides an abnormality identification device for a specific protein response curve, including a reaction vessel 10 , a light source 20 , an optical signal receiver 30 and a data processing device 50 .
反应容器10用于容纳待测样本,例如可以是透明的反应容器10。The reaction container 10 is used for containing the sample to be tested, and can be, for example, a transparent reaction container 10 .
光源20作为散射比浊法使用的光源20,其用于向反应容器10内的待测样本提供激光。The light source 20 is used as the light source 20 used in the nephelometric method, and is used for providing laser light to the sample to be measured in the reaction vessel 10 .
光信号接收器30设置在激光经待测样本形成的散射光的光路上,其用于采集散射光,并将散射光的光信号转换为电信号。The optical signal receiver 30 is disposed on the optical path of the scattered light formed by the laser light through the sample to be tested, and is used for collecting the scattered light and converting the optical signal of the scattered light into an electrical signal.
数据处理装置50与光信号接收器30信号连接,其用于根据电信号获取待测样本的特定蛋白反应曲线,如图3所示的特定蛋白反应曲线用于表示采样总时间内得到的电压随特定蛋白浓度的单调变化。The data processing device 50 is signally connected to the optical signal receiver 30, which is used to obtain the specific protein response curve of the sample to be tested according to the electrical signal. The specific protein response curve shown in FIG. Monotonic changes in the concentration of a specific protein.
取到的待测样本的特定蛋白反应曲线的公式,包括:The formula of the specific protein response curve of the sample to be tested, including:
V a=F(t a)。 Va = F( ta ).
其中,0≤t a≤T a,t a∈实数,t a为待测样本的采样时间,V a为采样时获取的电压,T a为采样总时间的结束时间点。一些实施例中,可对该曲线进行平滑处理(例如均值平滑或中值平滑),从而得到更加平滑的反应曲线,有助于后续的计算(对曲线的特征提取)。 Among them, 0≤t a ≤T a , ta ∈ real number, t a is the sampling time of the sample to be tested, Va is the voltage obtained during sampling, and T a is the end time point of the total sampling time. In some embodiments, the curve may be smoothed (for example, mean smoothing or median smoothing), so as to obtain a smoother response curve, which is helpful for subsequent calculation (feature extraction of the curve).
而后获取待测样本的特定蛋白反应曲线的一阶导数F’(t a)的最小值minF’(t a),根据一阶导数的最小值与预设阈值的关系,识别待测样本的特定蛋白反应曲线是否存在异常。一些实施例中,该预设阈值为零,如果minF’(t a)大于等于零,代表待测样本的特定蛋白反应曲线为一增函数,待测样本的特定蛋白反应曲线不存在异常,如果minF’(t a)小于零,待测样本的特定蛋白反应曲线存在异常。 Then, obtain the minimum value minF'(t a ) of the first derivative F'(t a ) of the specific protein response curve of the sample to be tested, and identify the specific sample to be tested according to the relationship between the minimum value of the first derivative and the preset threshold. Whether the protein response curve is abnormal. In some embodiments, the preset threshold is zero. If minF'(t a ) is greater than or equal to zero, it means that the specific protein response curve of the sample to be tested is an increasing function, and there is no abnormality in the specific protein response curve of the sample to be tested. '(t a ) is less than zero, the specific protein response curve of the sample to be tested is abnormal.
在待测样本的特定蛋白反应曲线存在异常时,并不意味着该特定蛋白反应曲线就要完全舍弃,本实施例中,还获取待测样本的特定蛋白反应曲线的二阶导数,根据二阶导数确定采样总时间内中的采样有效时间,而后根据采样有效时间的长度确定异常类型,具体的,数据处理装置50获取待测样本的特定蛋白反应曲线的二阶导数F”(t a),根据二阶导数确定采样有效时间。采样有效时间内待测样本的特定蛋白反应曲线需要满足F”(t a)小于零。并且,0≤t 1≤t 2≤T a,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点。如图4(箭头指向特定蛋白反应曲线处为波动异常处)所示,通常,满足上述条件的时间段只有一段。如果该时间段有两段或两段以上,选取时间长度最大的时间段作为采样有效时间,例如如图5所示,一满足上述条件的时间段的长度(t' 2-t' 1)较 小,就不作为采样有效时间。在其他实施例中,也可以根据其他规则选择采样有效时间。 When the specific protein response curve of the sample to be tested is abnormal, it does not mean that the specific protein response curve should be completely discarded. In this embodiment, the second derivative of the specific protein response curve of the sample to be tested is also obtained. The derivative determines the effective sampling time in the total sampling time, and then determines the abnormality type according to the length of the effective sampling time. Specifically, the data processing device 50 obtains the second derivative F'' (t a ) of the specific protein response curve of the sample to be tested, The effective time of sampling is determined according to the second derivative. The specific protein response curve of the sample to be tested within the effective time of sampling needs to satisfy that F”(t a ) is less than zero. In addition, 0≤t 1 ≤t 2 ≤T a , t 1 is the start time point of the effective sampling time, and t 2 is the end time point of the effective sampling time. As shown in Figure 4 (where the arrow points to the specific protein response curve is the abnormal fluctuation), usually, there is only one period of time that satisfies the above conditions. If there are two or more segments in the time segment, select the time segment with the largest time length as the sampling valid time. For example, as shown in FIG. If it is small, it will not be used as the valid sampling time. In other embodiments, the sampling valid time can also be selected according to other rules.
得到采样有效时间后,数据处理装置50根据采样有效时间的长度确定异常类型。本实施例中,异常类型有两类,第一类是特定蛋白反应曲线存在波动异常,代表着特定蛋白反应曲线并不严格单调递增,但是还是有具有后续能够用于计算的曲线部分,第二类是特定蛋白通道异常,该类异常意味着本次获得的特定蛋白曲线偏差严重而作废。具体的判断标准可以是:数据处理装置50获取采样有效时间与采样总时间的比例,将该比例与预设阈值P进行比较,如果采样有效时间大于预设阈值P,则特定蛋白反应曲线存在波动异常,如果采样有效时间小于预设阈值P,则特定蛋白反应曲线存在特定蛋白通道异常。例如,P的取值可以从40%至60%,以50%为例,当采样有效时间与采样总时间的比例超过50%,也就是说,在采样总时间内连续一半的时间特定蛋白反应曲线不存在异常,认定该曲线仍有部分可用。After obtaining the effective sampling time, the data processing device 50 determines the abnormality type according to the length of the effective sampling time. In this embodiment, there are two types of abnormality. The first type is that the specific protein response curve has abnormal fluctuations, which means that the specific protein response curve is not strictly monotonically increasing, but there are still curve parts that can be used for subsequent calculations. The class is an abnormality of a specific protein channel, which means that the specific protein curve obtained this time has a serious deviation and is invalid. The specific judgment criteria may be: the data processing device 50 obtains the ratio of the sampling effective time to the total sampling time, and compares the ratio with the preset threshold P, if the sampling effective time is greater than the preset threshold P, then the specific protein response curve fluctuates Abnormal, if the effective sampling time is less than the preset threshold P, the specific protein response curve has an abnormal specific protein channel. For example, the value of P can be from 40% to 60%, taking 50% as an example, when the ratio of the effective sampling time to the total sampling time exceeds 50%, that is, the specific protein reaction is continuously half of the total sampling time. There is no abnormality in the curve, and it is determined that the curve is still partially available.
在确定好异常类型后,数据处理装置50会输出与异常类型相关联的报警信息,例如,在特定蛋白反应曲线存在波动异常时,输出文字信息“特定蛋白反应曲线存在波动异常”,在特定蛋白通道异常时,输出文字信息“特定蛋白通道异常”。并且,当特定蛋白反应曲线存在波动异常,数据处理装置50可根据采样有效时间内的特定蛋白反应曲线计算出待测样本的特定蛋白浓度,而如果特定蛋白通道异常,则数据处理装置50不根据该特定蛋白反应曲线进行计算,或者屏蔽之前根据该曲线得到的检测结果。After the abnormality type is determined, the data processing device 50 will output alarm information associated with the abnormality type. For example, when there is an abnormal fluctuation in the specific protein response curve, the text message "There is a fluctuation abnormality in the specific protein response curve" is output. When the channel is abnormal, the text message "Specific protein channel is abnormal" is output. In addition, when there is an abnormal fluctuation in the specific protein response curve, the data processing device 50 can calculate the specific protein concentration of the sample to be tested according to the specific protein response curve within the sampling valid time, and if the specific protein channel is abnormal, the data processing device 50 does not The specific protein response curve is calculated, or the detection results obtained from the curve are masked before.
通过上述异常识别装置,能够有效识别异常的反应曲线,并能根据异常类型的不同输出不同的报警信息,以及后续采取不同的处理步骤,针对性和实用性更强。The abnormal response curve can be effectively identified by the above abnormality identification device, and different alarm information can be output according to different types of the abnormality, and different processing steps can be taken subsequently, which is more pertinent and practical.
在本实施例中,当特定蛋白反应曲线不存在异常或者存在波动异常,都可以根据特定蛋白反应曲线计算待测样本的特定蛋白浓度,下面对计算方式进行说明,在下列计算中,由异常识别装置对数据进行处理得到待测样本的特定蛋白反应浓度,在其他实施例中,也可以将得到的特定蛋白反应曲线输出给浓度计算装置,由浓度计算装置得到结果。In this embodiment, when there is no abnormality or abnormal fluctuation in the specific protein response curve, the specific protein concentration of the sample to be tested can be calculated according to the specific protein response curve. The calculation method is described below. In the following calculation, the abnormal The identification device processes the data to obtain the specific protein response concentration of the sample to be tested. In other embodiments, the obtained specific protein response curve can also be output to the concentration calculation device, and the concentration calculation device obtains the result.
在所举的计算实例中,异常识别装置还包括存储装置40,其用于存储各已知浓度样本的特定蛋白浓度和上述基于散射比浊法得到的对应的特定蛋白反应曲线。In the given calculation example, the abnormality identification device further includes a storage device 40, which is used for storing the specific protein concentration of each known concentration sample and the corresponding specific protein response curve obtained based on the nephelometric method.
一些实施例中,已知浓度样本的数目为N个,即具有N个按浓度梯度排列的已知浓度样本B 1,B 2,…,B i,…,B N;其中,第i个已知浓度样本的特定蛋白 浓度为C i,且0<C 1<C 2<…<C i<…<C N,1≤i≤N。 In some embodiments, the number of known concentration samples is N, that is, there are N known concentration samples B 1 , B 2 , . . . , B i , . The specific protein concentration of the sample with known concentration is C i , and 0<C 1 <C 2 <…<C i <…<C N , 1≤i≤N.
第i个已知浓度样本的定蛋白反应曲线的公式为:The formula of the fixed protein response curve of the i-th known concentration sample is:
V bi=F i(t b)。 V bi =Fi (t b ).
其中,0≤t b≤T b,t b∈实数,t b为已知浓度样本的采样时间,V bi为第i个已知浓度样本采样时获取的电压,T b为已知浓度样本的采样总时间的结束时间点。 Among them, 0≤t b ≤T b , t b ∈ real number, t b is the sampling time of the known concentration sample, V bi is the voltage obtained when the ith known concentration sample is sampled, T b is the known concentration sample The end time point of the total sampling time.
一些实施例中,对于任一已知浓度样本的特定蛋白反应曲线,还判断已知浓度样本的特定蛋白反应曲线是否存在异常,如果存在异常,则对存在异常的特定蛋白反应曲线的已知浓度样本重新检测,以再次获取相应的特定蛋白反应曲线,直到每个已知浓度样本的特定蛋白反应曲线均不存在异常。对于第i个已知浓度样本Bi,判断其特定蛋白反应曲线是否存在异常的方式,可以是:获取第i个已知浓度样本的特定蛋白反应曲线的一阶导数F i (t b),然后获取一阶导数F i’(t b)的最小值minF i’(t b),如果minF i’(t b)不小于零,则第i个已知浓度样本的特定蛋白反应曲线不存在异常,否则,第i个已知浓度样本的特定蛋白反应曲线存在异常,那么就再次对该已知浓度样本进行检测,直到该已知浓度样本的特定蛋白反应曲线的一阶导数不小于0。 In some embodiments, for the specific protein response curve of any sample with a known concentration, it is also determined whether the specific protein response curve of the known concentration sample is abnormal, and if there is an abnormality, the known concentration of the abnormal specific protein response curve is determined. The sample is re-tested to obtain the corresponding specific protein response curve again, until the specific protein response curve of each known concentration sample has no abnormality. For the i-th known concentration sample Bi, the way of judging whether the specific protein response curve of the i-th known concentration sample is abnormal can be: obtaining the first derivative F i of the specific protein response curve of the i-th known concentration sample , (t b ), Then obtain the minimum value minFi '(t b ) of the first derivative Fi '(t b ), if minFi '(t b ) is not less than zero, the specific protein response curve of the ith known concentration sample does not exist Otherwise, the specific protein response curve of the ith known concentration sample is abnormal, then the known concentration sample is detected again until the first derivative of the specific protein response curve of the known concentration sample is not less than 0.
如果待测样本的特定蛋白反应曲线不存在异常,在采样总时间内选取提取时间段,如果存在波动异常,在采样有效时间内选取提取时间段,提取时间段是用于提取曲线特征的时间段。获取到提取时间段后,数据处理装置50提取待测样本的特定蛋白反应曲线在提取时间段对应的曲线特征。If there is no abnormality in the specific protein response curve of the sample to be tested, select the extraction time period within the total sampling time. If there is fluctuation abnormality, select the extraction time period within the effective sampling time. The extraction time period is the time period used to extract curve features. . After acquiring the extraction time period, the data processing device 50 extracts the curve characteristics corresponding to the specific protein response curve of the sample to be tested in the extraction time period.
一些实施例中,如图3所示,待测样本的特定蛋白反应曲线不存在异常,提取待测样本的特定蛋白反应曲线在提取时间段对应的曲线特征,包括:In some embodiments, as shown in FIG. 3 , there is no abnormality in the specific protein response curve of the sample to be tested, and the curve characteristics corresponding to the specific protein response curve of the sample to be tested during the extraction time period are extracted, including:
计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的电压差D a1,电压差D a1的计算公式包括: Calculate the voltage difference D a1 between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested. The calculation formula of the voltage difference D a1 includes:
D a1=F(t a2)-F(t a1)。 D a1 =F(t a2 )-F(t a1 ).
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,0≤t a1<t a2≤T a,T a为采样总时间的结束时间点,将电压差D a1作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, 0≤t a1 <t a2 ≤T a , T a is the end time point of the total sampling time, the voltage difference D a1 is used as the curve characteristic of the specific protein response curve of the sample to be tested.
在另一些实施例中,如图3所示不存在异常,计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的面积S a1,面积S a1的计算公式包括: In other embodiments, there is no abnormality as shown in FIG. 3 , the area S a1 between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested is calculated, and the calculation formula of the area S a1 include:
Figure PCTCN2021092453-appb-000001
Figure PCTCN2021092453-appb-000001
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,0≤t a1<t a2≤T a,T a为采样总时间的结束时间点,将面积S a1作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, 0≤t a1 <t a2 ≤T a , and T a is the end time point of the total sampling time. a1 is used as the curve characteristic of the specific protein response curve of the sample to be tested.
一些实施例中,如图4或图5(箭头指向特定蛋白反应曲线处为波动处)所示,待测样本的特定蛋白反应曲线存在波动异常,提取待测样本的特定蛋白反应曲线在提取时间段对应的曲线特征,包括:In some embodiments, as shown in FIG. 4 or FIG. 5 (where the arrow points to the specific protein response curve is the fluctuation), the specific protein response curve of the sample to be tested has abnormal fluctuations, and the specific protein response curve of the sample to be extracted is extracted at the extraction time. Curve features corresponding to the segment, including:
计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的电压差D a2,电压差D a2的计算公式包括: Calculate the voltage difference D a2 between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested. The calculation formula of the voltage difference D a2 includes:
D a2=F(t a2)-F(t a1)。 D a2 =F(t a2 )-F(t a1 ).
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,t 1≤t a1<t a2≤t 2,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点,将电压差D a2作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, t 1 ≤t a1 <t a2 ≤t 2 , t 1 is the start time point of the effective sampling time, t 2 is the end time point of the effective time of sampling, and the voltage difference D a2 is taken as the curve characteristic of the specific protein response curve of the sample to be tested.
在另一些实施例中,如图4或图5(箭头指向特定蛋白反应曲线处为波动处)所示存在波动异常,计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的面积S a2,面积S a2的计算公式包括: In other embodiments, as shown in FIG. 4 or FIG. 5 (where the arrow points to the specific protein response curve is the fluctuation), there is an abnormal fluctuation, and calculate the starting time point and the extraction time point on the specific protein response curve of the sample to be tested. The area S a2 between the end time points, the calculation formula of the area S a2 includes:
Figure PCTCN2021092453-appb-000002
Figure PCTCN2021092453-appb-000002
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,t 1≤t a1<t a2≤t 2,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点,将面积S a2作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, t 1 ≤t a1 <t a2 ≤t 2 , t 1 is the start time point of the effective sampling time, t 2 is the end time point of the effective time of sampling, and the area S a2 is taken as the curve characteristic of the specific protein response curve of the sample to be tested.
而后,根据存储装置40中存储的N个已知浓度样本的特定蛋白反应曲线,获取各已知浓度样本的特定蛋白反应曲线在提取时间段对应的曲线特征r 1,r 2,…,r i,…,r N,1≤i≤N,r i为第i个已知浓度样本的特定蛋白反应曲线在提取时间段对应的曲线特征。 Then, according to the specific protein response curves of the N samples of known concentration stored in the storage device 40, the curve characteristics r 1 , r 2 , . ,...,r N , 1≤i≤N, r i is the curve characteristic corresponding to the specific protein response curve of the i-th known concentration sample in the extraction time period.
一些实施例中,对于第i个已知浓度样本Bi,计算已知浓度样本的特定蛋白反应曲线上不同两点间的电压差,以获取电压差D bi,电压差D bi的计算公式包括: In some embodiments, for the i-th known concentration sample Bi, the voltage difference between two different points on the specific protein response curve of the known concentration sample is calculated to obtain the voltage difference D bi , and the calculation formula of the voltage difference D bi includes:
D bi=F i(t b2)-F i(t b1)。 D bi =Fi (t b2 ) -Fi ( t b1 ).
其中,t b1和t b2是第i个已知浓度样本的特定蛋白反应曲线上两点的采样时间,0≤t b1<t b2≤T b,D bi为电压差,T b为已知浓度样本的采样总时间的结束时间点,如果待测样本的曲线特征为D a1或D a2,则取t b2=t a2,t b1=t a1,将电压差D bi作为第i个已知浓度样本的特定蛋白反应曲线的曲线特征r iAmong them, t b1 and t b2 are the sampling times of two points on the specific protein response curve of the i-th sample with known concentration, 0≤t b1 <t b2 ≤T b , D bi is the voltage difference, and T b is the known concentration The end time point of the total sampling time of the sample, if the curve characteristic of the sample to be tested is D a1 or D a2 , then take t b2 =t a2 , t b1 =t a1 , and take the voltage difference Dbi as the i-th known concentration The curve characteristic ri of the specific protein response curve of the sample.
一些实施例中,对于第i个已知浓度样本Bi,计算已知浓度样本的特定蛋 白反应曲线上不同两点间的面积,以获取面积S bi,面积S bi的计算公式包括: In some embodiments, for the i-th known concentration sample Bi, the area between two different points on the specific protein response curve of the known concentration sample is calculated to obtain the area S bi , and the calculation formula of the area S bi includes:
Figure PCTCN2021092453-appb-000003
Figure PCTCN2021092453-appb-000003
其中,S bi为已知浓度样本的特定蛋白反应曲线上不同两点间的面积,t b1和t b2是已知浓度样本的特定蛋白反应曲线上两点的采样时间,0≤t b1<t b2≤T b,T b为已知浓度样本采样总时间的结束时间点,如果待测样本的曲线特征为S a1或S a2,则取t b2=t a2,t b1=t a1,将面积S bi作为第i个已知浓度样本的特定蛋白反应曲线的曲线特征r iAmong them, S bi is the area between two different points on the specific protein response curve of the sample with known concentration, t b1 and t b2 are the sampling time of two points on the specific protein response curve of the sample with known concentration, 0≤t b1 <t b2 ≤T b , T b is the end time point of the total sampling time of the sample with known concentration, if the curve characteristic of the sample to be tested is S a1 or S a2 , then take t b2 =t a2 , t b1 =t a1 , take the area S bi as the curve characteristic r i of the specific protein response curve of the ith sample of known concentration.
提取到每个已知浓度样本的特定蛋白反应曲线的特征值后,将每个已知浓度样本的特定蛋白反应曲线的特征值与其对应的特定蛋白浓度建立数学函数对应关系,其中,将第i个已知浓度样本的特定蛋白反应曲线的特征值r i与其对应的特定蛋白浓度C i建立数学函数对应关系,1≤i≤N,进而获取定标函数关系式:r=F(C),其中,C为已知浓度样本的特定蛋白浓度,r为已知浓度样本的特定蛋白反应曲线的特征值。 After extracting the eigenvalues of the specific protein response curve of each known concentration sample, establish a mathematical function correspondence between the eigenvalues of the specific protein response curve of each known concentration sample and its corresponding specific protein concentration. The eigenvalue ri of a specific protein response curve of a sample of known concentration and its corresponding specific protein concentration C i establish a mathematical function corresponding relationship, 1≤i≤N, and then obtain the scaling function relationship: r=F(C), Among them, C is the specific protein concentration of the sample with known concentration, and r is the characteristic value of the specific protein response curve of the sample with known concentration.
得到待测样本的特定蛋白反应曲线的曲线特征后,数据处理装置50将待测样本的曲线特征输入定标函数关系式中,从而得到一个特定蛋白浓度,将该特定蛋白浓度作为待测样本的特定蛋白浓度。After obtaining the curve characteristics of the specific protein response curve of the sample to be tested, the data processing device 50 inputs the curve characteristics of the sample to be tested into the calibration function relationship, so as to obtain a specific protein concentration, which is used as the specific protein concentration of the sample to be tested. specific protein concentration.
实施例二 Embodiment 2
请参照图2,本实施例中提供了一种特定蛋白反应曲线的异常识别装置,包括反应容器10、光源20、光信号接收器30和数据处理装置50。Referring to FIG. 2 , this embodiment provides an abnormality identification device for a specific protein response curve, including a reaction vessel 10 , a light source 20 , an optical signal receiver 30 and a data processing device 50 .
反应容器10用于容纳待测样本,例如可以是透明的反应容器10。The reaction container 10 is used for containing the sample to be tested, and can be, for example, a transparent reaction container 10 .
光源20作为透射比浊法使用的光源20,其用于向反应容器10内的待测样本提供激光。The light source 20 is used as the light source 20 used in the nephelometric method, and is used for providing laser light to the sample to be tested in the reaction vessel 10 .
光信号接收器30设置在激光经待测样本形成的透射光的光路上,其用于采集透射光,并将透射光的光信号转换为电信号。The optical signal receiver 30 is disposed on the optical path of the transmitted light formed by the laser through the sample to be tested, and is used for collecting the transmitted light and converting the optical signal of the transmitted light into an electrical signal.
数据处理装置50与光信号接收器30信号连接,其用于根据电信号获取待测样本的特定蛋白反应曲线,如图6所示的特定蛋白反应曲线用于表示采样总时间内得到的电压随特定蛋白浓度的单调变化。The data processing device 50 is signally connected to the optical signal receiver 30, which is used to obtain the specific protein response curve of the sample to be tested according to the electrical signal. The specific protein response curve shown in FIG. Monotonic changes in the concentration of a specific protein.
取到的待测样本的特定蛋白反应曲线的公式,包括:The formula of the specific protein response curve of the sample to be tested, including:
V a=F(t a)。 Va = F( ta ).
其中,0≤t a≤T a,t a∈实数,t a为待测样本的采样时间,V a为采样时获取的电压,T a为采样总时间的结束时间点。一些实施例中,可对该曲线进行平滑处理(例如均值平滑或中值平滑),从而得到更加平滑的反应曲线,有助于后续的 计算(对曲线的特征提取)。 Among them, 0≤t a ≤T a , ta ∈ real number, t a is the sampling time of the sample to be tested, Va is the voltage obtained during sampling, and T a is the end time point of the total sampling time. In some embodiments, the curve may be smoothed (for example, mean smoothing or median smoothing), so as to obtain a smoother response curve, which is helpful for subsequent calculation (feature extraction of the curve).
而后获取待测样本的特定蛋白反应曲线的一阶导数F’(t a)的最大值max(F'(t a)),根据一阶导数的最大值与预设阈值的关系,识别待测样本的特定蛋白反应曲线是否存在异常。一些实施例中,该预设阈值为零,如果max(F'(t a))小于等于零,代表待测样本的特定蛋白反应曲线为一减函数,待测样本的特定蛋白反应曲线不存在异常,如果max(F'(t a))大于零,待测样本的特定蛋白反应曲线存在异常。 Then obtain the maximum value max(F'(t a )) of the first derivative F'(t a ) of the specific protein response curve of the sample to be tested, and identify the maximum value of the first derivative according to the relationship between the maximum value of the first derivative and the preset threshold. Whether there is any abnormality in the specific protein response curve of the sample. In some embodiments, the preset threshold is zero. If max(F'(t a )) is less than or equal to zero, it means that the specific protein response curve of the sample to be tested is a decreasing function, and the specific protein response curve of the sample to be tested is not abnormal. , if max(F'(t a )) is greater than zero, the specific protein response curve of the sample to be tested is abnormal.
在待测样本的特定蛋白反应曲线存在异常时,并不意味着该特定蛋白反应曲线就要完全舍弃,本实施例中,还获取待测样本的特定蛋白反应曲线的二阶导数,根据二阶导数确定采样总时间内中的采样有效时间,而后根据采样有效时间的长度确定异常类型,具体的,数据处理装置50获取待测样本的特定蛋白反应曲线的二阶导数F”(t a),根据二阶导数确定采样有效时间。采样有效时间内待测样本的特定蛋白反应曲线需要满足F”(t a)大于零。并且,0≤t 1≤t 2≤T a,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点。如图7(箭头指向特定蛋白反应曲线处为波动处)所示,通常,满足上述条件的时间段只有一段。如果该时间段有两段或两段以上,选取时间长度最大的时间段作为采样有效时间,例如如图8所示,一满足上述条件的时间段的长度(t' 2-t' 1)较小,就不作为采样有效时间。在其他实施例中,也可以根据其他规则选择采样有效时间。 When the specific protein response curve of the sample to be tested is abnormal, it does not mean that the specific protein response curve should be completely discarded. In this embodiment, the second derivative of the specific protein response curve of the sample to be tested is also obtained. The derivative determines the effective sampling time in the total sampling time, and then determines the abnormality type according to the length of the effective sampling time. Specifically, the data processing device 50 obtains the second derivative F'' (t a ) of the specific protein response curve of the sample to be tested, The effective time of sampling is determined according to the second derivative. The specific protein response curve of the sample to be tested within the effective time of sampling needs to satisfy that F”(t a ) is greater than zero. In addition, 0≤t 1 ≤t 2 ≤T a , t 1 is the start time point of the effective sampling time, and t 2 is the end time point of the effective sampling time. As shown in Fig. 7 (where the arrow points to the specific protein response curve is the fluctuation), generally, there is only one time period that satisfies the above conditions. If there are two or more segments in the time segment, select the time segment with the largest time length as the sampling valid time. For example, as shown in FIG. If it is small, it will not be used as the valid sampling time. In other embodiments, the sampling valid time can also be selected according to other rules.
得到采样有效时间后,数据处理装置50根据采样有效时间的长度确定异常类型。本实施例中,异常类型有两类,第一类是特定蛋白反应曲线存在波动异常,代表着特定蛋白反应曲线并不严格单调递减,但是还是有具有后续能够用于计算的曲线部分,第二类是特定蛋白通道异常,该类异常意味着本次获得的特定蛋白曲线偏差严重而作废。具体的判断标准可以是:After obtaining the effective sampling time, the data processing device 50 determines the abnormality type according to the length of the effective sampling time. In this embodiment, there are two types of abnormality. The first type is that the specific protein response curve has abnormal fluctuations, which means that the specific protein response curve is not strictly monotonically decreasing, but there are still curve parts that can be used for subsequent calculations. The class is an abnormality of a specific protein channel, which means that the specific protein curve obtained this time has a serious deviation and is invalid. The specific judgment criteria can be:
具体的判断标准可以是:数据处理装置50获取采样有效时间与采样总时间的比例,将该比例与预设阈值P进行比较,如果采样有效时间大于预设阈值P,则特定蛋白反应曲线存在波动异常,如果采样有效时间小于预设阈值P,则特定蛋白反应曲线存在特定蛋白通道异常。例如,P的取值可以从40%至60%,以50%为例,当采样有效时间与采样总时间的比例超过50%,也就是说,在采样总时间内连续一半的时间特定蛋白反应曲线不存在异常,认定该曲线仍有部分可用。The specific judgment criteria may be: the data processing device 50 obtains the ratio of the sampling effective time to the total sampling time, and compares the ratio with the preset threshold P, if the sampling effective time is greater than the preset threshold P, then the specific protein response curve fluctuates Abnormal, if the effective sampling time is less than the preset threshold P, the specific protein response curve has an abnormal specific protein channel. For example, the value of P can be from 40% to 60%, taking 50% as an example, when the ratio of the effective sampling time to the total sampling time exceeds 50%, that is, the specific protein reaction is continuously half of the total sampling time. There is no abnormality in the curve, and it is determined that the curve is still partially available.
在确定好异常类型后,数据处理装置50会输出与异常类型相关联的报警信息,例如,在特定蛋白反应曲线存在波动异常时,输出文字信息“特定蛋白反应曲线存在波动异常”,在特定蛋白通道异常时,输出文字信息“特定蛋白通道 异常”。并且,当特定蛋白反应曲线存在波动异常,数据处理装置50可根据采样有效时间内的特定蛋白反应曲线计算出待测样本的特定蛋白浓度,而如果特定蛋白通道异常,则数据处理装置50不根据该特定蛋白反应曲线进行计算,或者屏蔽之前根据该曲线得到的检测结果。After the abnormality type is determined, the data processing device 50 will output alarm information associated with the abnormality type. For example, when there is an abnormal fluctuation in the specific protein response curve, the text message "There is a fluctuation abnormality in the specific protein response curve" is output. When the channel is abnormal, the text message "Specific protein channel is abnormal" is output. In addition, when there is an abnormal fluctuation in the specific protein response curve, the data processing device 50 can calculate the specific protein concentration of the sample to be tested according to the specific protein response curve within the sampling valid time, and if the specific protein channel is abnormal, the data processing device 50 does not The specific protein response curve is calculated, or the detection results obtained from the curve are masked before.
通过上述异常识别装置,能够有效识别异常的反应曲线,并能根据异常类型的不同输出不同的报警信息,以及后续采取不同的处理步骤,针对性和实用性更强。The abnormal response curve can be effectively identified by the above abnormality identification device, and different alarm information can be output according to different types of the abnormality, and different processing steps can be taken subsequently, which is more pertinent and practical.
在本实施例中,当特定蛋白反应曲线不存在异常或者存在波动异常,都可以根据特定蛋白反应曲线计算待测样本的特定蛋白浓度,下面对计算方式进行说明,在下列计算中,由异常识别装置对数据进行处理得到待测样本的特定蛋白反应浓度,在其他实施例中,也可以将得到的特定蛋白反应曲线输出给浓度计算装置,由浓度计算装置得到结果。In this embodiment, when there is no abnormality or abnormal fluctuation in the specific protein response curve, the specific protein concentration of the sample to be tested can be calculated according to the specific protein response curve. The calculation method is described below. In the following calculation, the abnormal The identification device processes the data to obtain the specific protein response concentration of the sample to be tested. In other embodiments, the obtained specific protein response curve can also be output to the concentration calculation device, and the concentration calculation device obtains the result.
在所举的计算实例中,异常识别装置还包括存储装置40,其用于存储各已知浓度样本的特定蛋白浓度和上述基于透射比浊法得到的对应的特定蛋白反应曲线。In the given calculation example, the abnormality identification device further includes a storage device 40, which is used for storing the specific protein concentration of each known concentration sample and the corresponding specific protein response curve obtained based on the turbidimetric method.
一些实施例中,已知浓度样本的数目为N个,即具有N个按浓度梯度排列的已知浓度样本B 1,B 2,…,B i,…,B N;其中,第i个已知浓度样本的特定蛋白浓度为C i,且0<C 1<C 2<…<C i<…<C N,1≤i≤N。 In some embodiments, the number of known concentration samples is N, that is, there are N known concentration samples B 1 , B 2 , . . . , B i , . The specific protein concentration of the sample with known concentration is C i , and 0<C 1 <C 2 <…<C i <…<C N , 1≤i≤N.
第i个已知浓度样本的定蛋白反应曲线的公式为:The formula of the fixed protein response curve of the i-th known concentration sample is:
V bi=F i(t b)。 V bi =Fi (t b ).
其中,0≤t b≤T b,t b∈实数,t b为已知浓度样本的采样时间,V bi为第i个已知浓度样本采样时获取的电压,T b为已知浓度样本的采样总时间的结束时间点。 Among them, 0≤t b ≤T b , t b ∈ real number, t b is the sampling time of the known concentration sample, V bi is the voltage obtained when the ith known concentration sample is sampled, T b is the known concentration sample The end time point of the total sampling time.
一些实施例中,对于任一已知浓度样本的特定蛋白反应曲线,还判断已知浓度样本的特定蛋白反应曲线是否存在异常,如果存在异常,则对存在异常的特定蛋白反应曲线的已知浓度样本重新检测,以再次获取相应的特定蛋白反应曲线,直到每个已知浓度样本的特定蛋白反应曲线均不存在异常。对于第i个已知浓度样本Bi,判断其特定蛋白反应曲线是否存在异常的方式,可以是:In some embodiments, for the specific protein response curve of any sample of known concentration, it is also determined whether the specific protein response curve of the known concentration sample is abnormal, and if there is abnormality, the known concentration of the abnormal specific protein response curve is determined. The sample is re-tested to obtain the corresponding specific protein response curve again, until the specific protein response curve of each known concentration sample has no abnormality. For the i-th known concentration sample Bi, the way to judge whether the specific protein response curve is abnormal can be:
获取第i个已知浓度样本的特定蛋白反应曲线的一阶导数F i’(t b),然后获取一阶导数F i’(t b)的最大值max(F i'(t b)),如果max(F i'(t b))不大于零,则第i个已知浓度样本的特定蛋白反应曲线不存在异常,否则,第i个已知浓度样本的特定蛋白反应曲线存在异常,那么就再次对该已知浓度样本进行检测,直到该已知浓度样本的特定蛋白反应曲线的一阶导数的最大值不大于0。 Obtain the first derivative F i '(t b ) of the specific protein response curve for the ith sample of known concentration, and then obtain the maximum value of the first derivative F i '(t b ) max(F i '(t b )) , if max(Fi '(t b )) is not greater than zero, the specific protein response curve of the i -th known concentration sample is not abnormal, otherwise, the specific protein response curve of the i-th known concentration sample is abnormal, Then, the known concentration sample is tested again until the maximum value of the first derivative of the specific protein response curve of the known concentration sample is not greater than 0.
如果待测样本的特定蛋白反应曲线不存在异常,在采样总时间内选取提取时间段,如果存在波动异常,在采样有效时间内选取提取时间段,提取时间段是用于提取曲线特征的时间段。获取到提取时间段后,数据处理装置50提取待测样本的特定蛋白反应曲线在提取时间段对应的曲线特征。If there is no abnormality in the specific protein response curve of the sample to be tested, select the extraction time period within the total sampling time. If there is fluctuation abnormality, select the extraction time period within the effective sampling time. The extraction time period is the time period used to extract curve features. . After acquiring the extraction time period, the data processing device 50 extracts the curve characteristics corresponding to the specific protein response curve of the sample to be tested in the extraction time period.
一些实施例中,如图6所示,待测样本的特定蛋白反应曲线不存在异常,提取待测样本的特定蛋白反应曲线在提取时间段对应的曲线特征,包括:In some embodiments, as shown in FIG. 6 , there is no abnormality in the specific protein response curve of the sample to be tested, and the curve characteristics corresponding to the specific protein response curve of the sample to be tested during the extraction time period are extracted, including:
计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的电压差的绝对值|D a1|,电压差的绝对值|D a1|的计算公式包括: Calculate the absolute value of the voltage difference |D a1 | between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested. The calculation formula of the absolute value of the voltage difference |D a1 | includes:
|D a1|=|F(t a2)-F(t a1)|。 |D a1 |=|F(t a2 )-F(t a1 )|.
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,0≤t a1<t a2≤T a,T a为采样总时间的结束时间点,将电压差的绝对值|D a1|作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, 0≤t a1 <t a2 ≤T a , T a is the end time point of the total sampling time, the voltage difference The absolute value of |D a1 | is used as the curve characteristic of the specific protein response curve of the sample to be tested.
在另一些实施例中,如图6所示不存在异常,计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的面积S a1,面积S a1的计算公式包括: In other embodiments, there is no abnormality as shown in FIG. 6 , the area S a1 between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested is calculated, and the calculation formula of the area S a1 include:
Figure PCTCN2021092453-appb-000004
Figure PCTCN2021092453-appb-000004
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,0≤t a1<t a2≤T a,T a为采样总时间的结束时间点,将面积S a1作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, 0≤t a1 <t a2 ≤T a , and T a is the end time point of the total sampling time. a1 is used as the curve characteristic of the specific protein response curve of the sample to be tested.
一些实施例中,如图7或图8(箭头指向特定蛋白反应曲线处为波动处)所示,待测样本的特定蛋白反应曲线存在波动异常,提取待测样本的特定蛋白反应曲线在提取时间段对应的曲线特征,包括:In some embodiments, as shown in FIG. 7 or FIG. 8 (where the arrow points to the specific protein response curve is the fluctuation), the specific protein response curve of the sample to be tested has abnormal fluctuations, and the specific protein response curve of the sample to be extracted is extracted at the extraction time. Curve features corresponding to the segment, including:
计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的电压差的绝对值|D a2|,电压差的绝对值|D a2|的计算公式包括: Calculate the absolute value of the voltage difference |D a2 | between the start time point and the end time point of the extraction time period on the specific protein response curve of the sample to be tested. The calculation formula of the absolute value of the voltage difference |D a2 | includes:
|D a2|=|F(t a2)-F(t a1)|。 |D a2 |=|F(t a2 )-F(t a1 )|.
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,t 1≤t a1<t a2≤t 2,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点,将电压差的绝对值|D a2|作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, t 1 ≤t a1 <t a2 ≤t 2 , t 1 is the start time point of the effective sampling time, t 2 is the end time point of the effective sampling time, and the absolute value of the voltage difference |D a2 | is used as the curve characteristic of the specific protein response curve of the sample to be tested.
在另一些实施例中,如图7或图8(箭头指向特定蛋白反应曲线处为波动处)所示存在波动异常,计算待测样本的特定蛋白反应曲线上提取时间段的起始时间点和结束时间点间的面积S a2,面积S a2的计算公式包括: In other embodiments, as shown in FIG. 7 or FIG. 8 (where the arrow points to the specific protein response curve is the fluctuation), there is an abnormal fluctuation, the starting time point of the extraction time period on the specific protein response curve of the sample to be tested and the The area S a2 between the end time points, the calculation formula of the area S a2 includes:
Figure PCTCN2021092453-appb-000005
Figure PCTCN2021092453-appb-000005
其中,t a1为提取时间段的起始时间点,t a2为提取时间段的结束时间点,t 1≤t a1<t a2≤t 2,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点,将面积S a2作为待测样本的特定蛋白反应曲线的曲线特征。 Among them, t a1 is the start time point of the extraction time period, t a2 is the end time point of the extraction time period, t 1 ≤t a1 <t a2 ≤t 2 , t 1 is the start time point of the effective sampling time, t 2 is the end time point of the effective time of sampling, and the area S a2 is taken as the curve characteristic of the specific protein response curve of the sample to be tested.
而后,根据存储装置40中存储的N个已知浓度样本的特定蛋白反应曲线,获取各已知浓度样本的特定蛋白反应曲线在提取时间段对应的曲线特征r 1,r 2,…,r i,…,r N,1≤i≤N,r i为第i个已知浓度样本的特定蛋白反应曲线在提取时间段对应的曲线特征。 Then, according to the specific protein response curves of the N samples of known concentration stored in the storage device 40, the curve characteristics r 1 , r 2 , . ,...,r N , 1≤i≤N, r i is the curve characteristic corresponding to the specific protein response curve of the i-th known concentration sample in the extraction time period.
一些实施例中,对于第i个已知浓度样本Bi,计算已知浓度样本的特定蛋白反应曲线上不同两点间的电压差的绝对值,以获取电压差的绝对值|D bi|,电压差的绝对值|D bi|的计算公式包括: In some embodiments, for the i-th known concentration sample Bi, the absolute value of the voltage difference between two different points on the specific protein response curve of the known concentration sample is calculated to obtain the absolute value of the voltage difference |D bi |, voltage The formula for calculating the absolute value of the difference |D bi | includes:
|D bi|=|F i(t b2)-F i(t b1)|。 |D bi |=|Fi (t b2 ) -Fi ( t b1 )|.
其中,t b1和t b2是第i个已知浓度样本的特定蛋白反应曲线上两点的采样时间,0≤t b1<t b2≤T b,|D bi|为电压差的绝对值,T b为已知浓度样本的采样总时间的结束时间点,如果待测样本的曲线特征为|D a1|或|D a2|,则取t b2=t a2,t b1=t a1,将电压差的绝对值|D bi|作为第i个已知浓度样本的特定蛋白反应曲线的曲线特征r iAmong them, t b1 and t b2 are the sampling times of two points on the specific protein response curve of the ith known concentration sample, 0≤t b1 <t b2 ≤T b , |D bi | is the absolute value of the voltage difference, T b is the end time point of the total sampling time of the sample with known concentration. If the curve characteristic of the sample to be tested is | D a1 | or |D a2 | The absolute value of |D bi | as the curve characteristic r i of the specific protein response curve of the ith sample of known concentration.
一些实施例中,对于第i个已知浓度样本Bi,计算已知浓度样本的特定蛋白反应曲线上不同两点间的面积,以获取面积S bi,面积S bi的计算公式包括: In some embodiments, for the i-th known concentration sample Bi, the area between two different points on the specific protein response curve of the known concentration sample is calculated to obtain the area S bi , and the calculation formula of the area S bi includes:
Figure PCTCN2021092453-appb-000006
Figure PCTCN2021092453-appb-000006
其中,S bi为已知浓度样本的特定蛋白反应曲线上不同两点间的面积,t b1和t b2是已知浓度样本的特定蛋白反应曲线上两点的采样时间,0≤t b1<t b2≤T b,T b为已知浓度样本采样总时间的结束时间点,如果待测样本的曲线特征为S a1或S a2,则取t b2=t a2,t b1=t a1,将面积S bi作为第i个已知浓度样本的特定蛋白反应曲线的曲线特征r iAmong them, S bi is the area between two different points on the specific protein response curve of the sample with known concentration, t b1 and t b2 are the sampling time of two points on the specific protein response curve of the sample with known concentration, 0≤t b1 <t b2 ≤T b , T b is the end time point of the total sampling time of the sample with known concentration, if the curve characteristic of the sample to be tested is S a1 or S a2 , then take t b2 =t a2 , t b1 =t a1 , take the area S bi as the curve characteristic r i of the specific protein response curve of the ith sample of known concentration.
提取到每个已知浓度样本的特定蛋白反应曲线的特征值后,将每个已知浓度样本的特定蛋白反应曲线的特征值与其对应的特定蛋白浓度建立数学函数对应关系,其中,将第i个已知浓度样本的特定蛋白反应曲线的特征值r i与其对应的特定蛋白浓度C i建立数学函数对应关系,1≤i≤N,进而获取定标函数关系式:r=F(C),其中,C为已知浓度样本的特定蛋白浓度,r为已知浓度样本的特定蛋白反应曲线的特征值。 After extracting the eigenvalues of the specific protein response curve of each known concentration sample, establish a mathematical function correspondence between the eigenvalues of the specific protein response curve of each known concentration sample and its corresponding specific protein concentration. The eigenvalue ri of a specific protein response curve of a sample of known concentration and its corresponding specific protein concentration C i establish a mathematical function corresponding relationship, 1≤i≤N, and then obtain the scaling function relationship: r=F(C), Among them, C is the specific protein concentration of the sample with known concentration, and r is the characteristic value of the specific protein response curve of the sample with known concentration.
得到待测样本的特定蛋白反应曲线的曲线特征后,数据处理装置50将待测样本的曲线特征输入定标函数关系式中,从而得到一个特定蛋白浓度,将该特 定蛋白浓度作为待测样本的特定蛋白浓度。After obtaining the curve characteristics of the specific protein response curve of the sample to be tested, the data processing device 50 inputs the curve characteristics of the sample to be tested into the calibration function relationship, so as to obtain a specific protein concentration, which is used as the specific protein concentration of the sample to be tested. specific protein concentration.
实施例三Embodiment 3
本实施例提供了一种特定蛋白反应曲线的异常识别方法,如图9所示,包括步骤:This embodiment provides an abnormal identification method for a specific protein response curve, as shown in Figure 9, including steps:
步骤100、在预设的采样总时间内对待测样本进行特定蛋白检测,以获取待测样本的特定蛋白反应曲线。待测样本的特定蛋白反应曲线在采样总时间内为单调函数。Step 100: Perform specific protein detection on the sample to be tested within a preset total sampling time to obtain a specific protein response curve of the sample to be tested. The specific protein response curve of the sample to be tested is a monotonic function over the total sampling time.
检测的方式包括基于散射比浊法在预设的采样总时间内对待测样本进行特定蛋白检测以及基于透射比浊法在预设的采样总时间内对待测样本进行特定蛋白检测,如果基于散射比浊法对待测样本进行特定蛋白检测,得到的曲线为如图3所示的增函数,如果基于透射比浊法对待测样本进行特定蛋白检测,得到的曲线为如图6所示的减函数。两种检测方式可用同一公式表达特定蛋白反应曲线,该公式为:The detection methods include specific protein detection of the sample to be tested within a preset total sampling time based on nephelometric method and specific protein detection of the sample to be tested based on nephelometric method within a preset total sampling time. The turbidimetric method is used to detect the specific protein of the sample to be tested, and the obtained curve is an increasing function as shown in Figure 3. If the specific protein detection of the sample to be tested is performed based on the transmission turbidimetric method, the obtained curve is a decreasing function as shown in Figure 6. The two detection methods can express a specific protein response curve using the same formula, which is:
V a=F(t a)。 Va = F( ta ).
其中,0≤t a≤T a,t a∈实数,t a为待测样本的采样时间,V a为采样时获取的电压,T a为采样总时间的结束时间点。 Among them, 0≤t a ≤T a , ta ∈ real number, t a is the sampling time of the sample to be tested, Va is the voltage obtained during sampling, and T a is the end time point of the total sampling time.
步骤200、获取待测样本的特定蛋白反应曲线的一阶导数。Step 200: Obtain the first derivative of the specific protein response curve of the sample to be tested.
步骤300,根据一阶导数识别特定蛋白反应曲线是否存在异常,如果存在异常,执行步骤400,如果不存在异常,可执行步骤600。 Step 300 , according to the first derivative, identify whether there is an abnormality in the specific protein response curve, if there is an abnormality, go to step 400 , and if there is no abnormality, go to step 600 .
一些实施例中,基于散射比浊法获取待测样本的特定蛋白反应曲线,判断一阶导数的最小值minF’(t a)是否小于零,如果小于零,则特定蛋白反应曲线存在异常。 In some embodiments, the specific protein response curve of the sample to be tested is obtained based on the nephelometric method, and it is determined whether the minimum value minF '(ta) of the first derivative is less than zero. If it is less than zero, the specific protein response curve is abnormal.
一些实施例中,基于透射比浊法获取待测样本的特定蛋白反应曲线,则判断一阶导数的最大值max(F'(t a))是否大于零,如果大于零,则特定蛋白反应曲线存在异常。 In some embodiments, the specific protein response curve of the sample to be tested is obtained based on the turbidimetric method, and it is determined whether the maximum value max(F'(t a )) of the first derivative is greater than zero, and if it is greater than zero, the specific protein response curve is determined. There is an exception.
步骤400、获取待测样本的特定蛋白反应曲线的二阶导数,根据特定蛋白反应曲线的二阶导数确定异常类型。Step 400: Obtain the second derivative of the specific protein response curve of the sample to be tested, and determine the abnormality type according to the second derivative of the specific protein response curve.
在待测样本的特定蛋白反应曲线存在异常时,并不意味着该特定蛋白反应曲线就要完全舍弃,本实施例中,还获取待测样本的特定蛋白反应曲线的二阶导数,根据二阶导数确定采样总时间内中的采样有效时间,而后根据采样有效时间的长度确定异常类型,具体的,获取待测样本的特定蛋白反应曲线的二阶导数F″(t a),根据二阶导数确定采样有效时间。 When the specific protein response curve of the sample to be tested is abnormal, it does not mean that the specific protein response curve should be completely discarded. In this embodiment, the second derivative of the specific protein response curve of the sample to be tested is also obtained. The derivative determines the effective sampling time in the total sampling time, and then determines the abnormality type according to the length of the effective sampling time. Specifically, the second derivative F″(t a ) of the specific protein response curve of the sample to be tested is obtained, and according to the second derivative Determine the sampling valid time.
一些实施例中,基于散射比浊法获取待测样本的特定蛋白反应曲线,采样 有效时间内待测样本的特定蛋白反应曲线需要满足F″(t a)小于零,并且,0≤t 1≤t 2≤T a,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点。 In some embodiments, the specific protein response curve of the sample to be tested is obtained based on the nephelometric method, and the specific protein response curve of the sample to be tested within the valid sampling period needs to satisfy that F″(t a ) is less than zero, and 0≤t 1 ≤ t 2 ≤T a , t 1 is the start time point of the effective sampling time, and t 2 is the end time point of the effective sampling time.
一些实施例中,基于透射比浊法获取待测样本的特定蛋白反应曲线,采样有效时间内待测样本的特定蛋白反应曲线需要满足F″(t a)大于零。并且,0≤t 1≤t 2≤T a,t 1为采样有效时间的起始时间点,t 2为采样有效时间的结束时间点。 In some embodiments, the specific protein response curve of the sample to be tested is obtained based on the turbidimetric method, and the specific protein response curve of the sample to be tested within the valid sampling period needs to satisfy that F″(t a ) is greater than zero. Moreover, 0≤t 1 ≤ t 2 ≤T a , t 1 is the start time point of the effective sampling time, and t 2 is the end time point of the effective sampling time.
如图4或7(箭头指向特定蛋白反应曲线处为波动处)所示,通常,满足上述条件的时间段只有一段。如果该时间段有两段或两段以上,选取时间长度最大的时间段作为采样有效时间,例如如图5或8所示,一满足上述条件的时间段的长度(t' 2-t' 1)较小,就不作为采样有效时间。在其他实施例中,也可以根据其他规则选择采样有效时间。 As shown in Figure 4 or 7 (where the arrow points to the specific protein response curve is the fluctuation), generally, there is only one period of time that satisfies the above conditions. If there are two or more segments in the time segment, select the time segment with the largest time length as the sampling valid time. ) is smaller, it will not be used as the effective sampling time. In other embodiments, the sampling valid time can also be selected according to other rules.
得到采样有效时间后,根据采样有效时间的长度确定异常类型。本实施例中,异常类型有两类,第一类是特定蛋白反应曲线存在波动异常,代表着特定蛋白反应曲线并不严格单调递减,但是还是有具有后续能够用于计算的曲线部分,第二类是特定蛋白通道异常,该类异常意味着本次获得的特定蛋白曲线偏差严重而作废。具体的判断标准可以是:After the valid sampling time is obtained, the abnormality type is determined according to the length of the valid sampling time. In this embodiment, there are two types of abnormality. The first type is that the specific protein response curve has abnormal fluctuations, which means that the specific protein response curve is not strictly monotonically decreasing, but there are still curve parts that can be used for subsequent calculations. The class is an abnormality of a specific protein channel, which means that the specific protein curve obtained this time has a serious deviation and is invalid. The specific judgment criteria can be:
具体的判断标准可以是:获取采样有效时间与采样总时间的比例,将该比例与预设阈值P进行比较,如果采样有效时间大于预设阈值P,则特定蛋白反应曲线存在波动异常,如果采样有效时间小于预设阈值P,则特定蛋白反应曲线存在特定蛋白通道异常。例如,P的取值可以从40%至60%,以50%为例,当采样有效时间与采样总时间的比例超过50%,也就是说,在采样总时间内连续一半的时间特定蛋白反应曲线不存在异常,认定该曲线仍有部分可用。The specific judgment criteria may be: obtaining the ratio of the effective sampling time to the total sampling time, and comparing the ratio with the preset threshold P. If the sampling effective time is greater than the preset threshold P, the specific protein response curve has abnormal fluctuations. If the effective time is less than the preset threshold P, the specific protein response curve has abnormal specific protein channel. For example, the value of P can be from 40% to 60%, taking 50% as an example, when the ratio of the effective sampling time to the total sampling time exceeds 50%, that is, the specific protein reaction is continuously half of the total sampling time. There is no abnormality in the curve, and it is determined that the curve is still partially available.
步骤500、输出与异常类型关联的异常报警信息。Step 500: Output abnormal alarm information associated with the abnormal type.
例如,在特定蛋白反应曲线存在波动异常时,输出文字信息“特定蛋白反应曲线存在波动异常”,在特定蛋白通道异常时,输出文字信息“特定蛋白通道异常”。并且,当特定蛋白反应曲线存在波动异常,可根据采样有效时间内的特定蛋白反应曲线计算出待测样本的特定蛋白浓度,而如果特定蛋白通道异常,则不根据该特定蛋白反应曲线进行计算,或者屏蔽之前根据该曲线得到的检测结果。基于散射比浊法得到特定蛋白反应曲线后,得到待测样本的特定蛋白浓度的计算方式可参照实施例一的描述,基于透射比浊法得到特定蛋白反应曲线后,得到待测样本的特定蛋白浓度的计算方式可参照实施例二的描述。For example, when there is an abnormal fluctuation in the response curve of a specific protein, the text information "There is an abnormal fluctuation in the response curve of a specific protein" is output, and when the specific protein channel is abnormal, the text information "Abnormality in the specific protein channel" is output. In addition, when there is an abnormal fluctuation in the specific protein response curve, the specific protein concentration of the sample to be tested can be calculated according to the specific protein response curve within the valid sampling period, and if the specific protein channel is abnormal, it is not calculated based on the specific protein response curve. Or mask the detection results obtained from the curve before. After obtaining the specific protein response curve based on nephelometric method, the calculation method of obtaining the specific protein concentration of the sample to be tested can refer to the description in Example 1. After obtaining the specific protein response curve based on the turbidimetric method, the specific protein concentration of the sample to be tested can be obtained. The calculation method of the concentration can refer to the description of the second embodiment.
步骤600、结束异常识别流程。结束异常识别流程,如果是基于散射比浊法得到特定蛋白反应曲线,得到待测样本的特定蛋白浓度的计算方式可参照实施例一的描述,如果是基于透射比浊法得到特定蛋白反应曲线,得到待测样本的 特定蛋白浓度的计算方式可参照实施例二的描述。Step 600: End the abnormality identification process. End the abnormality identification process. If the specific protein response curve is obtained based on nephelometric method, the calculation method to obtain the specific protein concentration of the sample to be tested can refer to the description in Example 1. If the specific protein response curve is obtained based on the turbidimetric method, For the calculation method to obtain the specific protein concentration of the sample to be tested, refer to the description of the second embodiment.
当特定蛋白反应曲线不存在异常时,检测结果的界面如图10所示,当特定蛋白反应曲线存在波动异常时,检测结果的界面如图11所示,左下角会同时显示检测结果和报警信息,当特定蛋白反应曲线存在特定蛋白通道异常时,检测结果的界面如图12所示,在该界面的左下角只显示有报警信息而屏蔽了检测结果。When there is no abnormality in the specific protein response curve, the detection result interface is shown in Figure 10. When the specific protein response curve fluctuates abnormally, the detection result interface is shown in Figure 11, and the detection result and alarm information will be displayed in the lower left corner at the same time. , when a specific protein channel is abnormal in the specific protein response curve, the interface of the detection result is shown in Figure 12. Only the alarm information is displayed in the lower left corner of the interface and the detection result is shielded.
需要说明的是,上述实施例一至三均以特定蛋白为例进行说明,在其他实施例中,当样本的采样曲线为单调函数时,均可采用上述实施例中相似的方式实现异常识别。It should be noted that the above-mentioned Embodiments 1 to 3 are all described by taking a specific protein as an example. In other embodiments, when the sampling curve of the sample is a monotonic function, the abnormality identification can be implemented in a similar manner as in the above-mentioned embodiment.
本领域技术人员可以理解,上述实施方式中各种方法的全部或部分功能可以通过硬件的方式实现,也可以通过计算机程序的方式实现。当上述实施方式中全部或部分功能通过计算机程序的方式实现时,该程序可以存储于一计算机可读存储介质中,存储介质可以包括:只读存储器、随机存储器、磁盘、光盘、硬盘等,通过计算机执行该程序以实现上述功能。例如,将程序存储在设备的存储器中,当通过处理器执行存储器中程序,即可实现上述全部或部分功能。另外,当上述实施方式中全部或部分功能通过计算机程序的方式实现时,该程序也可以存储在服务器、另一计算机、磁盘、光盘、闪存盘或移动硬盘等存储介质中,通过下载或复制保存到本地设备的存储器中,或对本地设备的***进行版本更新,当通过处理器执行存储器中的程序时,即可实现上述实施方式中全部或部分功能。Those skilled in the art can understand that all or part of the functions of the various methods in the foregoing embodiments may be implemented by means of hardware or by means of computer programs. When all or part of the functions in the above embodiments are implemented by means of a computer program, the program may be stored in a computer-readable storage medium, and the storage medium may include: read-only memory, random access memory, magnetic disk, optical disk, hard disk, etc. The computer executes the program to realize the above-mentioned functions. For example, the program is stored in the memory of the device, and when the program in the memory is executed by the processor, all or part of the above functions can be realized. In addition, when all or part of the functions in the above-mentioned embodiments are realized by means of a computer program, the program can also be stored in a server, another computer, a magnetic disk, an optical disk, a flash disk or a mobile hard disk and other storage media, and saved by downloading or copying All or part of the functions in the above embodiments can be implemented when the program in the memory is executed by the processor.
上述实施例中,通过特定蛋白反应曲线的一阶导数识别出是否有异常,又根据其二阶导数确定出异常的类型,再输出与所述异常类型关联的异常报警信息,整个过程高效快速,从而让用户不但快速知晓曲线的是否可用于后续的计算,还通过报警信息指示用户采取相应的应对措施。In the above embodiment, whether there is an abnormality is identified by the first-order derivative of the specific protein response curve, and the type of abnormality is determined according to its second-order derivative, and then the abnormality alarm information associated with the abnormality type is output. The whole process is efficient and fast, In this way, users can not only quickly know whether the curve can be used for subsequent calculations, but also instruct users to take corresponding countermeasures through alarm information.
以上应用了具体个例对本发明进行阐述,只是用于帮助理解本发明,并不用以限制本发明。对于本发明所属技术领域的技术人员,依据本发明的思想,还可以做出若干简单推演、变形或替换。The above specific examples are used to illustrate the present invention, which are only used to help understand the present invention, and are not intended to limit the present invention. For those skilled in the art to which the present invention pertains, according to the idea of the present invention, several simple deductions, modifications or substitutions can also be made.

Claims (10)

  1. 一种特定蛋白反应曲线的异常识别方法,其特征在于包括:A method for identifying abnormality of a specific protein response curve, characterized in that it comprises:
    在预设的采样总时间内对待测样本进行特定蛋白检测,以获取待测样本的特定蛋白反应曲线,所述待测样本的特定蛋白反应曲线在所述采样总时间内为单调函数;Perform specific protein detection on the sample to be tested within a preset total sampling time to obtain a specific protein response curve of the sample to be tested, and the specific protein response curve of the sample to be tested is a monotonic function within the total sampling time;
    获取所述待测样本的特定蛋白反应曲线的一阶导数;obtaining the first derivative of the specific protein response curve of the sample to be tested;
    根据所述一阶导数识别所述特定蛋白反应曲线是否存在异常;Identifying whether the specific protein response curve is abnormal according to the first derivative;
    如果所述特定蛋白反应曲线存在异常,获取所述待测样本的特定蛋白反应曲线的二阶导数,根据所述特定蛋白反应曲线的二阶导数确定异常类型;If the specific protein response curve is abnormal, obtain the second derivative of the specific protein response curve of the sample to be tested, and determine the abnormal type according to the second derivative of the specific protein response curve;
    输出与所述异常类型关联的异常报警信息。Exception alarm information associated with the exception type is output.
  2. 如权利要求1所述的特定蛋白反应曲线的异常识别方法,其特征在于,获取待测样本的特定蛋白反应曲线的方式,包括:The method for identifying abnormality of a specific protein response curve according to claim 1, wherein the method for obtaining the specific protein response curve of the sample to be tested comprises:
    基于散射比浊法在预设的采样总时间内对待测样本进行特定蛋白检测,以获取待测样本的特定蛋白反应曲线;或者Perform specific protein detection on the sample to be tested within a preset total sampling time based on nephelometry to obtain a specific protein response curve of the sample to be tested; or
    基于透射比浊法在预设的采样总时间内对待测样本进行特定蛋白检测,以获取待测样本的特定蛋白反应曲线。The specific protein detection of the sample to be tested is carried out in a preset total sampling time based on the turbidimetric method, so as to obtain a specific protein response curve of the sample to be tested.
  3. 如权利要求2所述的异常识别方法,其特征在于,所述根据所述一阶导数识别所述特定蛋白反应曲线是否存在异常,包括:The abnormality identification method according to claim 2, wherein the identifying whether the specific protein response curve is abnormal according to the first derivative comprises:
    如果基于散射比浊法获取待测样本的特定蛋白反应曲线,判断所述一阶导数的最小值是否小于零,如果小于零,则所述特定蛋白反应曲线存在异常;If the specific protein response curve of the sample to be tested is obtained based on the nephelometric method, it is determined whether the minimum value of the first derivative is less than zero, and if it is less than zero, the specific protein response curve is abnormal;
    如果基于透射比浊法获取待测样本的特定蛋白反应曲线,判断所述一阶导数的最大值是否大于零,如果大于零,则所述特定蛋白反应曲线存在异常。If the specific protein response curve of the sample to be tested is obtained based on the turbidimetric method, it is determined whether the maximum value of the first derivative is greater than zero, and if it is greater than zero, the specific protein response curve is abnormal.
  4. 如权利要求1所述的异常识别方法,其特征在于,根据所述二阶导数确定异常类型,包括:The abnormality identification method according to claim 1, wherein determining the abnormality type according to the second derivative comprises:
    根据所述二阶导数确定所述采样总时间内中的采样有效时间;determining the sampling effective time in the total sampling time according to the second derivative;
    根据所述采样有效时间的长度确定异常类型,所述异常类型包括特定蛋白反应曲线存在波动异常以及存在特定蛋白通道异常。The abnormality type is determined according to the length of the effective sampling time, and the abnormality type includes fluctuation abnormality in the response curve of a specific protein and abnormality in a specific protein channel.
  5. 如权利要求4所述的异常识别方法,其特征在于,所述根据所述二阶导数确定所述采样总时间内中的采样有效时间,包括:The abnormality identification method according to claim 4, wherein the determining the sampling effective time in the total sampling time according to the second order derivative comprises:
    如果基于散射比浊法获取待测样本的特定蛋白反应曲线,获取所述采样总时间内二阶导数小于零的至少一个时间段,根据预设规则将至少一个时间段中的一个时间段作为所述采样有效时间;If the specific protein response curve of the sample to be tested is obtained based on the nephelometric method, at least one time period in which the second-order derivative is less than zero in the total sampling time is obtained, and one time period in the at least one time period is used as the all time period according to the preset rule. The sampling effective time;
    如果基于透射比浊法获取待测样本的特定蛋白反应曲线,获取所述采样总时间内二阶导数大于零的至少一个时间段,根据预设规则将至少一个时间段中 的一个时间段作为所述采样有效时间;If the specific protein response curve of the sample to be tested is obtained based on the turbidimetric method, at least one time period in which the second-order derivative is greater than zero in the total sampling time is obtained, and one time period in the at least one time period is used as the all time period according to the preset rule. The sampling effective time;
    其中,根据预设规则将至少一个时间段中的一个时间段作为所述采样有效时间,包括:Wherein, according to a preset rule, one time period in at least one time period is used as the sampling effective time, including:
    将所述至少一个时间段中长度最大的时间段作为采样有效时间。The time segment with the longest length among the at least one time segment is used as the sampling valid time.
  6. 如权利要求5所述的异常识别方法,其特征在于,所述根据所述采样有效时间的长度识别所述特定蛋白反应曲线是否存在异常,包括:The abnormality identification method according to claim 5, wherein the identifying whether the specific protein response curve is abnormal according to the length of the effective sampling time comprises:
    获取所述采样有效时间与采样总时间的比例,将所述比例与预设阈值进行比较,如果所述采样有效时间大于预设阈值,则所述特定蛋白反应曲线存在波动异常,如果所述采样有效时间小于预设阈值,则所述特定蛋白反应曲线存在特定蛋白通道异常。Obtain the ratio of the sampling effective time to the total sampling time, and compare the ratio with a preset threshold. If the sampling effective time is greater than the preset threshold, the specific protein response curve has abnormal fluctuations. If the sampling If the effective time is less than the preset threshold, there is an abnormality of the specific protein channel in the specific protein response curve.
  7. 如权利要求1所述的异常识别方法,其特征在于,如果所述特定蛋白反应曲线存在波动异常,输出异常报警信息后,还包括:The abnormality identification method according to claim 1, wherein if the specific protein response curve has abnormal fluctuations, after outputting abnormal alarm information, the method further comprises:
    根据所述采样有效时间内的特定蛋白反应曲线计算得到待测样本的特定蛋白浓度。The specific protein concentration of the sample to be tested is calculated according to the specific protein response curve within the effective sampling period.
  8. 一种采样曲线的异常识别方法,其特征在于,包括:A method for identifying abnormality of sampling curves, comprising:
    在预设的采样总时间内对待测样本进行检测,以获取待测样本的采样曲线,所述待测样本的采样曲线在所述采样总时间内为单调函数;Detect the sample to be tested within a preset total sampling time to obtain a sampling curve of the sample to be tested, and the sampling curve of the sample to be tested is a monotonic function within the total sampling time;
    获取所述待测样本的采样曲线的一阶导数;obtaining the first derivative of the sampling curve of the sample to be tested;
    根据所述一阶导数识别所述采样曲线是否存在异常;Identifying whether the sampling curve is abnormal according to the first-order derivative;
    如果所述采样曲线存在异常,获取所述待测样本的采样曲线的二阶导数,根据所述采样曲线的二阶导数确定异常类型;If the sampling curve is abnormal, obtain the second-order derivative of the sampling curve of the sample to be tested, and determine the abnormality type according to the second-order derivative of the sampling curve;
    输出与所述异常类型关联的异常报警信息。Exception alarm information associated with the exception type is output.
  9. 一种特定蛋白反应曲线的异常识别装置,其特征在于包括:A device for identifying abnormality of a specific protein response curve, characterized in that it comprises:
    反应容器,用于容纳待测样本;a reaction vessel for containing the sample to be tested;
    光源,用于向所述反应容器内的待测样本提供激光;a light source for providing laser light to the sample to be tested in the reaction vessel;
    光信号接收器,用于采集激光经待测样本产生的光信号,并将所述光信号转换为电信号;an optical signal receiver, used to collect the optical signal generated by the laser through the sample to be tested, and convert the optical signal into an electrical signal;
    数据处理装置,与所述光信号接收器信号连接,用于:A data processing device, in signal connection with the optical signal receiver, for:
    根据所述电信号获取待测样本的特定蛋白反应曲线,所述待测样本的特定蛋白反应曲线用于表示采样总时间内得到的电压随特定蛋白浓度的单调变化;Obtain the specific protein response curve of the sample to be tested according to the electrical signal, and the specific protein response curve of the sample to be tested is used to represent the monotonic change of the voltage obtained in the total sampling time with the concentration of the specific protein;
    获取所述待测样本的特定蛋白反应曲线的一阶导数;obtaining the first derivative of the specific protein response curve of the sample to be tested;
    根据所述一阶导数识别所述特定蛋白反应曲线是否存在异常;Identifying whether the specific protein response curve is abnormal according to the first derivative;
    如果所述特定蛋白反应曲线存在异常,获取所述待测样本的特定蛋白反应 曲线的二阶导数,根据所述特定蛋白反应曲线的二阶导数确定异常类型;If the specific protein response curve is abnormal, obtain the second derivative of the specific protein response curve of the sample to be tested, and determine the abnormal type according to the second derivative of the specific protein response curve;
    输出与所述异常类型关联的异常报警信息。Exception alarm information associated with the exception type is output.
  10. 一种计算机可读存储介质,其特征在于,所述介质上存储有程序,所述程序能够被处理器执行以实现如权利要求1-8中任一项所述的方法。A computer-readable storage medium, characterized in that a program is stored on the medium, and the program can be executed by a processor to implement the method according to any one of claims 1-8.
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