Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention.
Referring to fig. 1, fig. 1 is a flowchart illustrating an embodiment of a method for calibrating a packed red blood cell volume according to the present invention, which includes the following steps:
s1: and applying voltage to the sample, recording the test temperature, the AD value of the hematocrit and the test current, converting the AD value into a sample resistance value, and calculating to obtain an initial hematocrit value through a correlation equation of the sample resistance value and the hematocrit value. In the step, voltages are applied to two ends of a prepared sample at different temperatures, AD values related to hematocrit Hct are converted into sample resistance values R through amplification logic operation of an internal circuit, and an initial hematocrit value Hct is obtained through calculation of a correlation equation of the sample resistance values R and the hematocrit value Hct0The correlation equation of the sample resistance value R and the hematocrit value Hct is as follows: k is1*x2+k2*x+k3(ii) a Wherein y is the initial hematocrit value Hct0X is resistance R, k1、k2、k3All the three are correlation equation coefficients; meanwhile, the corresponding test temperature T of the sample is recorded0And a test current I0。
S2: and determining the reference temperature and the reference hematocrit value, and obtaining a temperature difference value and a hematocrit difference value. In this step, the temperature difference Δ T is the test temperature T0With a reference temperature TCThe difference, i.e. Δ T ═ T0-TCThe hematocrit difference Δ Hct is the initial hematocrit value Hct0And the product of the standard hematocrit value HctCThe difference, i.e. Δ Hct ═ Hct0-HctCHct is usually determined as the packed normal human red blood cells range from about 30% to 55% with a mean of 42%C=42%。
S3: and substituting the temperature difference and the hematocrit difference into a compensation factor equation to obtain a compensation factor. In this step, the compensation factor equation is:
F=a+b*x+c*y+d*x2+e*y2+f*x*y+g*x3+h*y3+i*x*y2+j*x2y the compensation factor equation is obtained by fitting, wherein F is a compensation factor, and x and y are respectively a temperature difference value delta T, a hematocrit difference value delta Hct and a test current I0Any two of the three, a, b, c, d, e, F, g, h, i and j are compensation factor equation coefficients, and the temperature difference value delta T and the hematocrit difference value delta Hct are brought into the compensation factor equation to obtain a compensation factor F.
S4: and substituting the current value and the compensation factor into a current correction equation to obtain the correction current. In this step, the current correction equation is: i isc=I0F α, wherein IcTo correct the current, I0For testing current, F is compensation factor, alpha is current correction equation coefficient, and test current I0The compensation factor F is substituted into a current correction equation to obtain a correction current Ic。
S5: and substituting the correction current into a blood glucose concentration equation to obtain a blood glucose concentration correction value. In this step, the blood glucose concentration equation is:
y=u1*x4+u2*x3+u3*x2+u4*x+u5;
wherein y is the blood glucose concentration equation, x is the correction current, u1、u2、u3、u4、u5Are all blood glucose concentration equation coefficients. The blood glucose concentration equation coefficient is the above-mentioned reference temperature TCAnd the reference hematocrit value HctCAfter determining the blood glucose concentration equation, the correction current I in step S4 is obtained after fitting the standard parameterscAnd substituting the blood sugar concentration equation to obtain a blood sugar concentration correction value C.
Next, a specific calibration test was performed for blood samples of different temperatures and different hematocrit values by using the above hematocrit calibration method.
Example 1
This example compensates the blood glucose concentration reading for both temperature and hematocrit variables. Venous whole blood with the hematocrit of 20%, 30%, 42%, 55% and 70% is prepared firstly, and whole blood samples with the concentration of 2.8mmol/L, 5.6mmol/L, 13.9mmol/L, 19.4mmol/L, 25.0mmol/L and 33.3mmol/L are prepared for each vein of the hematocrit respectively, and the numerical calibration process is calibrated by a full-automatic biochemical analyzer in the present case. Then theSequentially testing the 30 venous whole blood samples at the environmental temperatures of 5 ℃, 15 ℃, 25 ℃, 35 ℃ and 45 ℃, respectively, repeatedly testing the same blood sample at the same temperature for 10 times, and calculating the average value to obtain the testing temperature T measured by the glucometer0The value of the electrical signal AD related to the hematocrit, and the test current I related to the blood glucose concentration0The test results are shown in tables 1 to 3:
TABLE 1 test Current I0Watch (A)
TABLE 2 AD values of hematocrit
TABLE 3 test temperature T0Watch (A)
Then, the step S1 is executed to convert the AD value into the phase of the hematocrit Hct according to the amplification and calculation logic of the test circuitThe sample resistance value R is closed, and the correlation equation of the sample resistance value R and the hematocrit Hct is k1*x2+k2*x+k3Calculating to obtain initial hematocrit value Hct0A value, wherein y is an initial hematocrit value Hct0X is resistance R, k1、k2、k3The three are all correlation equation coefficients, the correlation equation of R and Hct is obtained by fitting the data of R and Hct, and the equation in this embodiment is: hct% — 34.49x2+406.76x-1081.13, calculated as in table 4:
TABLE 4 initial hematocrit value Hct0Watch (A)
The above step S2 is executed, and the reference temperature T is set in the present embodimentC25 ℃ C, basis hematocrit HctC42%, calculate Δ T ═ T0-TCAnd Δ Hct ═ h (Hct)0-HctC) 100, the results are as follows:
TABLE 5 Δ T data sheet
TABLE 6 Δ Hct data Table
The above step S3 is executed to bring the temperature difference Δ T and the hematocrit difference Δ Hct into the compensation factor equation:
F=a+b*x+c*y+d*x2+e*y2+f*x*y+g*x3+h*y3+i*x*y2+j*x2y, wherein F is a compensation factor, x is a temperature difference value delta T, y is a hematocrit difference value delta Hct, and a, b, c, d, e, F, g, h, i and j are compensation factor equation coefficients to obtain a compensation factor F; after fitting, the compensation factor equation obtains the compensation factor equation coefficients as follows: a-0.9794, b-0.0552, c-1.0584E-02, d-1.9972E-04, E-7.5517E-05, f-2.7920E-04, g-7.8018E-06, h-4.3645E-06, i-8.1613E-06, j-8.3161E-06, and the fit coefficient is R2At 0.99, the compensation factor F is as follows:
TABLE 7 Compensation factor F Table
The above step S4 is executed to obtain the current value I0Correction equation I for the current introduced by the sum compensation factor Fc=I0*F*α,IcTo correct the current, I0To test the current, F is the compensation factor, α is the current correction equation coefficient, in this embodiment α is 0.001, and the correction current I is obtainedcThe following were used:
TABLE 8 correction Current Ic Table
Under the condition that the reference temperature is 25 ℃, the hematocrit of a reference blood sample is adjusted to 42% +/-2%, a Meirui BS-360E type full-automatic biochemical analyzer is used for establishing a blood glucose concentration equation in a fitting mode, the calibration value of the sample is y, the test current is x. The blood glucose concentration equation in this example 1 is specifically:
y=0.0014*x4-0.0449*x3+0.4343*x2+2.1963x+0.2637;
the above step S5 is executed to correct the current IcSubstituting the coding equation to obtain a corrected blood glucose concentration value C, and calculating the relative deviation between the corrected blood glucose concentration value C and the reading of the biochemical analyzer, the results are shown in Table 9a and Table 9 b:
TABLE 9a blood glucose concentration correction value C Table
TABLE 9b comparative table of relative deviation of corrected blood glucose concentration C from reading of biochemical analyzer
In the prior art, a step-by-step linear iterative fitting method is used for compensating the readings of the pressure and the temperature of the red blood cells, and a specific technical scheme is shown in patent CN 108195900A. Setting control experiments according to the method of the prior art, setting a constant temperature and humidity chamber at 10 ℃, 25 ℃ and 40 ℃, respectively, setting venous whole blood with anticoagulant at 30%, 42% and 60%, and using a full-automatic biochemical analyzer for calibration, setting blood samples at 2.8mmol/L, 5.6mmol/L, 15.3mmol/L and 29.2 mmol/L; comparing the blood glucose concentration value obtained by the fitting mode of the prior art with the reading of a biochemical analyzer to obtain the relative deviation based on the prior art at different temperatures as shown in tables 10-12:
TABLE 10 relative deviation Table based on the prior art at 10 deg.C
TABLE 11 relative deviation Table based on the prior art at 25 deg.C
TABLE 12 relative deviation Table based on the prior art at 40 deg.C
The comparison of the experimental results shows that the relative deviation a between the value obtained by the control experiment and the reading of the biochemical analyzer is more than 10% on average, the value obtained by the hematocrit correction method of the invention is compared with the reading of the biochemical analyzer, the relative deviation b is basically less than 5%, and the experimental results prove that the accuracy can be greatly improved by adopting the correction method of the invention, because the correction method adopted by the invention is polynomial fitting, and only one compensation factor equation is needed for calculating the compensation factor, the method effectively avoids the problem of large system error caused by multiple linear equation iterations in the prior art; meanwhile, the correction method of the invention is simpler, thereby greatly reducing the system operation amount.
Further, as for the application aspect of the invention, the correction method of the invention is mostly applied to portable blood glucose monitoring devices such as blood glucose test strips and the like, thereby enabling users to quickly and accurately obtain blood glucose readings; the method can be used for testing a plurality of standard blood samples with different hematocrit and different concentrations at different temperatures to obtain corresponding testing temperatures, AD values of the hematocrit and testing currents, corresponding blood glucose concentration readings are obtained by calculation according to the hematocrit correction method, a mapping table is established and stored in advance for the testing temperatures, the AD values of the hematocrit and the testing currents and the corresponding blood glucose concentration readings, when a user needs to measure blood glucose, the corresponding blood glucose concentration readings can be obtained by calling and searching the mapping table only by measuring the AD values of the testing temperatures and the hematocrit and testing current parameters, the operation process is further reduced, and the user can obtain the blood glucose concentration readings more quickly.
Example 2
This embodiment performs a compensation calculation of the glucose concentration reading with both temperature and current variables. Firstly, the hematocrit of the venous whole blood is configured to be 42% + -2%, and whole blood samples with blood glucose concentration of 2.8mmol/L, 5.6mmol/L, 9.4mmol/L, 15.3mmol/L and 27.8mmol/L are respectively configured. Then, the 7 venous whole blood samples were sequentially tested at ambient temperatures of 5 deg.C, 15 deg.C, 25 deg.C, 35 deg.C and 45 deg.C, the same blood sample was repeatedly tested at the same temperature for 10 times, and the average value was obtained to obtain the test temperature T measured by the glucometer0And a test current I related to the blood glucose concentration0The test results are shown in tables 9 and 10:
TABLE 13 test Current I0Watch (A)
TABLE 14 test temperature T0Watch (A)
The above step S2 is executed to set the reference temperature TC25 ℃ to obtain the product0-TC(ii) a The step S3 is executed to determine the temperature difference Δ T and the test current I0The compensation factor equation after the deformation is introduced: f ═ a + b x + c y + d x2+e*y2+f*x*y+g*x3+h*y3+i*x*y2+j*x2Y, wherein F is a compensation factor, x is a temperature difference value delta T, y is a hematocrit difference value delta Hct, and a, b, c, d, e, F, g, h, i and j are compensation factor equation coefficients to obtain a compensation factor F; after fitting, the compensation factor equation obtains the compensation factor equation coefficients as follows: a-1.0000, b-0.0201, c-2.9142E-03, d-1.2971E-04, E-1.6035E-07, f-3.1622E-05, g-5.1301E-05, h-1.3611E-11, i-5.5490E-10, j-5.6393E-07, and the coefficient of fit is R20.99; in the case of embodiment 2, the compensation factor F is the blood glucose concentration value, so the aforementioned steps S4 and S5 can be omitted, and the compensation factor equation is directly used to solve the initial current I0And temperature T0And substituting x and y serving as the compensation factor equation into the compensation factor equation to directly obtain the blood glucose concentration correction value C.
In order to determine the effectiveness of the correction method, the relative deviation of the blood glucose concentration correction value at other temperatures is calculated by taking the blood glucose concentration correction value at 25 ℃ as a standard, and a table 15 is obtained; meanwhile, in order to verify the accuracy of the calibration method, the reading of the biochemical analyzer is taken as a standard, and the relative deviation of the blood glucose concentration correction value and the blood glucose concentration correction value is calculated to obtain a table 16; it can be seen from tables 15 and 16 that the relative deviation generated by the present invention is small, which indicates that the above hematocrit correction method is also applicable to the distortion compensation calculation of both temperature and current variables.
Watch 15
TABLE 16
Further, for the application aspect of the present invention, a manner similar to the preset data mapping table in embodiment 1 may also be adopted in this embodiment, so that when the present invention is applied to a portable blood glucose monitoring device such as a blood glucose test strip, a user can quickly obtain a blood glucose concentration reading, which is not described herein again.
Example 3
This example compensates the blood glucose concentration reading for both the current and hematocrit variables. The test temperature was set to three constant temperature values of 10 deg.C, 25 deg.C, 40 deg.C, the positive and negative fluctuations of which did not exceed 2 deg.C, the hematocrit of anticoagulated venous whole blood was set to 20%, 30%, 42%, 55%, 70%, respectively, and the blood of each hematocrit was set to blood samples of 2.8mmol/L, 6.1mmol/L, 19.4mmol/L, 33.3 mmol/L. Then, the above blood samples were tested at three constant temperatures, and each blood sample was repeated 10 times to obtain a series of AD values and test current I0Executing step S1, converting the AD value into a sample resistance value R related to the hematocrit Hct according to the test circuit amplification operation logic, and according to the correlation equation y ═ k between the sample resistance value R and the hematocrit Hct1*x2+k2*x+k3Calculating to obtain initial hematocrit value Hct0A value, wherein y is an initial hematocrit value Hct0X is resistance R, k1、k2、k3All the three are correlation equation coefficients; the above step S2 is executed to set the reference hematocrit HctC42%, the hematocrit difference Δ Hct was calculated as Hct0-HctCThe results are shown in tables 17a, 17b and 17 c:
TABLE 17a hematocrit difference Δ Hct and test current I at 10 deg.C0Watch (A)
TABLE 17b hematocrit difference Δ Hct and test current I at 25 deg.C0Watch (A)
TABLE 17c hematocrit difference Δ Hct and test current I at 40 deg.C0Watch (A)
Executing the above step S3 to obtain the hematocrit difference Δ Hct and the test current I0The compensation factor equation after the deformation is introduced:
F=a+b*x+c*y+d*x2+e*y2+f*x*y+g*x3+h*y3+i*x*y2+j*x2y, obtaining a compensation factor F, wherein x is the hematocrit difference value delta Hct, and y is the test current I0The coefficient of determinability at the time of fitting is R2After fitting, the compensation factor equation yields the compensation factor equation coefficients at three constant temperatures, as shown in table 18.
TABLE 18 Compensation factor equation coefficients and decision coefficient tables
Coefficient of compensation factor equation
|
10℃
|
25℃
|
40℃
|
a
|
3.0825
|
1.0540
|
-1.4863
|
b
|
-0.2041
|
-0.1385
|
-0.0873
|
c
|
-0.2373
|
1.5875
|
2.2639
|
d
|
-0.0052
|
-0.0009
|
0.0026
|
e
|
0.5500
|
0.2520
|
0.0836
|
f
|
0.1629
|
0.1205
|
0.0739
|
g
|
0.0002
|
3.3e-06
|
5.7e-05
|
h
|
-0.0268
|
-0.0128
|
-0.0035
|
i
|
-0.0106
|
-0.0054
|
-0.0014
|
j
|
0.0005
|
0.0005
|
0.0004
|
Coefficient of determinability R2 |
0.99
|
0.99
|
0.99 |
At this time, the compensation factor F at different temperatures is the blood glucose concentration value at the temperature according to the initial current I0And the hematocrit difference value delta Hct to directly obtain the blood glucose concentration correction value C. In order to determine the correction precision, the blood glucose concentration correction value C calculated by the hematocrit correction method is compared with the reading of a biochemical analyzer to obtain corresponding relative deviation; meanwhile, a comparison experiment is set, the blood glucose concentration value obtained by the fitting mode in the prior art is compared with the reading of a biochemical analyzer to obtain corresponding relative deviation, and as shown in tables 19a, 19b and 19c, the relative basic maintenance of the blood glucose concentration value generated by the method is within 10 percent, the deviation is very small, and the method for correcting the hematocrit is also suitable for the deformation compensation calculation conditions of two variables of temperature and current.
TABLE 19a relative deviation of the corrected blood glucose concentration value C from the reading of the biochemical analyzer at 10 deg.C
TABLE 19b blood glucose concentration correction C at 25 deg.C vs. Biochemical Analyzer readings
TABLE 19a relative deviation of the corrected blood glucose concentration value C from the reading of the biochemical analyzer at 40 deg.C
Further, for the application aspect of the present invention, a manner similar to the preset data mapping table in embodiment 1 may also be adopted in this embodiment, so that when the present invention is applied to a portable blood glucose monitoring device such as a blood glucose test strip, a user can quickly obtain a blood glucose concentration reading, which is not described herein again.
It should be noted that, when the compensation factor is calculated in the hematocrit correction method of the present invention, the parameter variables are the temperature difference Δ T, the hematocrit difference Δ Hct, and the test current I0Any two of the three are used, and then the correction factor is used for calculating the blood glucose concentration correction value C, in other embodiments, the variables and the weight in the calculation process of the compensation factor can be adaptively adjusted according to the actual situation, and the adjustment is not limited herein; in addition, the scheme of the invention is not only suitable for the portable blood sugar monitoring devices such as the blood sugar test strip and the like, but also suitable for uric acid, lactic acid, cholesterol and the likeThe test strip for measuring the concentration of the redox metabolite in the plasma is not limited herein.
The invention provides a erythrocyte backlog correction method which is different from the prior art, reduces the correction steps of blood sugar test and obviously reduces the error of blood sugar test.
Another solution provided by the present invention is: there is provided a storage medium having stored therein program data executable to implement any of the aforementioned red blood cell backlog correction methods. The storage medium of the present invention for storing program data relating to the aforementioned hematocrit correction method for performing the aforementioned hematocrit correction method may include: various media capable of storing program codes, such as a U disk, a removable hard disk, a Read Only Memory (ROM), a Random Access Memory (RAM), a magnetic disk, or an optical disk.
In contrast to the state of the art, the present invention also provides a storage medium for storing program data relating to the aforementioned hematocrit correction method, by which correction steps of a blood glucose test are reduced and blood glucose test errors are significantly reduced.
It should be noted that the above embodiments belong to the same inventive concept, and the description of each embodiment has a different emphasis, and reference may be made to the description in other embodiments where the description in individual embodiments is not detailed.
The above-mentioned embodiments only express the embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.