TWI470226B - Methods for compensating a blood glucose concentration - Google Patents

Description

Method of compensating blood glucose concentration

The present invention relates to a method of compensating for blood glucose concentration, and more particularly to a method of compensating for blood glucose concentration in a hematocrit ratio.

Electrochemical Sensor Strips have been used to detect various substances in fluids. The basic principle is to use a chemical reagent (Reagent) to generate one analyte to be analyzed. An electrochemical action to generate an electrical output signal associated with the analyte to be measured. When the fluid to be tested is human blood and the analyte is blood sugar, a glucose oxidase and other complexes can be used as a chemical reagent.

Hematocrit (HCT) refers to the proportion of red blood cells contained in a given amount of blood. In general, the blood volume ratio of male blood is about 36 to 50%, and the blood volume ratio of female blood is about 34 to 47%. According to the blood cell volume ratio in the blood, people can understand the quality of blood. In addition, when measuring the blood glucose concentration, the blood glucose concentration measurement will also vary with the blood cell volume ratio.

Figure 1 is a graph showing the relationship between the measured value of blood glucose concentration measured by a conventional blood glucose meter and the actual value of blood glucose concentration at different hematocrit ratios. The vertical axis of Fig. 1 is a measurement of the blood glucose concentration measured by the blood glucose meter, and the horizontal axis of Fig. 1 is the actual value of the blood glucose concentration. As shown in Fig. 1, when the hematocrit ratio (for example, 60%) is greater than 41% based on the hematocrit ratio of 41%, the measured value of blood glucose concentration (300 mg/dL) is lower than the actual value of the blood glucose concentration ( 400 mg/dL). Conversely, when the hematocrit ratio (eg 20%) is less than 41%, the measured blood glucose concentration (500 mg/dL) is higher than the actual value of the blood glucose concentration (400 mg/dL). Therefore, in order to obtain the actual value of the blood glucose concentration, it is necessary to measure the blood cell volume ratio in advance, and compensate the blood glucose concentration measurement value according to the blood cell volume ratio, thereby obtaining the blood glucose concentration value when the blood cell volume ratio is about 41%. .

There are many methods for measuring the volume ratio of blood cells, for example, a method of measuring blood impedance; an optical method; a redox reaction; and an electrochemical method to obtain a blood cell volume ratio. The European Patent Application Publication No. EP 1 707 953 A1 discloses a method for determining the hematocrit ratio by means of a redox reaction. According to the measurement method, in the electrochemical sensing test piece, a redox substance must be provided on the counter electrode to generate a significant redox current to measure the relevant hematocrit ratio.

There are also many methods for compensating the blood glucose concentration by the hematocrit ratio, for example, U.S. Patent Nos. 7,771,583, 7,288,174 and 6,377,896, and U.S. Patent Publication No. 2008/0105568. In the prior art, a method for compensating for blood glucose concentration by using a table lookup method and an interpolation method is disclosed. It is a group of data that is experimentally performed using known samples, and the measurement results are recorded in a table. Table 1 shows the voltage values obtained by measuring the blood glucose concentration (G50~G600) samples using a blood glucose meter when different hematocrit ratios (Ht) are used.

When compensating for the blood glucose concentration, it is necessary to obtain an estimated value of the blood cell volume ratio of the sample to be tested in advance, and then find the corresponding group according to the measured value of the sample to be tested measured by the blood glucose machine. The estimated value of the hematocrit ratio is 39, and the measured value of the sample to be tested is 45V as an example. As shown in Table 2 below, the corresponding group may have a hematocrit ratio of 35 and 45 and a blood glucose concentration of G50 and G100.

Then use the interpolation method to obtain the voltage x and G100 voltage y of G50 when the hematocrit ratio is 39, and then obtain the measured value of x, y and the sample to be tested is 45V, and the blood cell volume ratio of the sample to be tested is the standard value. The compensation value z at (standard). Finally, using the proportional distribution and z, the blood glucose concentration when the hematocrit ratio of the sample to be tested is the standard value is obtained (not shown in Table 2).

However, there is still room for improvement in the method of compensating blood glucose concentration by the hematocrit ratio according to the prior art.

It is an object of an embodiment of the present invention to provide a method of compensating for blood glucose concentration. It is an object of an embodiment of the present invention to provide a method for easily compensating for blood glucose concentration.

According to an embodiment of the present invention, a method for compensating for a blood glucose concentration is provided, which uses an electrochemical measuring device including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece to measure one of the electrodes. The blood glucose concentration compensation value of the blood is measured. The method of compensating for blood glucose concentration includes the following steps. Using a plurality of sample blood having different and known hematocrit ratios and actual blood glucose concentrations, the blood glucose concentration measurements of the blood samples are measured, and the blood glucose concentration actual values and blood glucose concentration measurements are determined based on the samples. A relationship between the relationship and the volume of the blood cells is determined to obtain at least a first relationship. Supply through the electrodes A predetermined voltage is applied to the blood to be tested, and an electrical signal is generated to measure the blood glucose concentration measurement value of the blood to be tested according to the electrical signal. The blood glucose concentration compensation value of the blood to be tested is calculated according to the blood glucose concentration measurement value of the blood to be tested, the blood volume ratio of the blood to be tested, and the at least one first relational expression.

According to an embodiment of the present invention, a method for compensating blood glucose concentration is provided, which uses a sensing test piece including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece to measure one of the electrodes. The blood glucose concentration compensation value of the blood to be tested. The method of compensating for blood glucose concentration includes the following steps. A plurality of sample blood having different and known hematocrit ratios and actual blood glucose concentration values are prepared, and blood glucose concentration measurements of the blood of the samples are measured. According to the known hematocrit ratio and the actual value of the blood glucose concentration of the sample blood, and the blood glucose concentration measurement value of the blood of the samples, the blood samples of the samples are obtained by linear regression method. A second relationship between the actual value of blood glucose concentration and the measured value of blood glucose concentration. The second relationship is linear and at least one first relation is obtained according to the slope of the second relationship and the hematocrit ratio of the sample blood. A predetermined voltage is supplied to the blood to be tested through the electrodes, and an electrical signal is generated to measure the blood glucose concentration measurement value of the blood to be tested according to the electrical signal. The blood glucose concentration compensation value of the blood to be tested is calculated according to the blood glucose concentration measurement value of the blood to be tested, the blood volume ratio of the blood to be tested, and the at least one first relational expression.

In an embodiment, the at least one first relationship may be a plurality of linear relationships. In an embodiment, the at least one first relationship may be a linear relationship.

According to an embodiment of the invention, only a plurality of sets of equations need to be stored in the memory of the electrochemical measuring device, the storage capacity used is small, and a large number of selection operations are not required, and at least the first one is In only one embodiment of the relational expression, the selection operation is not required, so that the calculation load of the processor of the electrochemical measuring device can be reduced, and the electrochemical measuring device can operate smoothly, without taking too much time for calculation.

Other objects and advantages of the present invention will become apparent from the technical features disclosed herein. The above and other objects, features, and advantages of the invention will be apparent from

2 is a functional block diagram of an electrochemical measuring device in accordance with an embodiment of the present invention. As shown in FIG. 2, the sensing test strip 200 includes two working electrodes 211 and 212. The electrochemical measuring device 100 includes one or two connectors 111 and 112, a reference voltage source 120, a current-voltage conversion circuit 130, an analog-to-digital conversion circuit 140, a processor 150, and a display 160. In an embodiment, a memory 170 may further be included. The connecting portions 111 and 112 are adapted to electrically connect the working electrodes 211 and 212, respectively. The reference voltage source 120 can be a ground terminal. The working electrode 211 is electrically connected to the reference voltage source 120 through the connection portion 111, and the working electrode 212 is electrically connected to the analog digital conversion circuit 140, the current-voltage conversion circuit 130, and the processor 150 through the connection portion 112. Display 160 is electrically coupled to processor 150. The memory 170 can store a plurality of linear relationships or data for the processor 150 to use the linear relationship data to calculate a more accurate blood glucose concentration based on the hematocrit ratio (described later).

During operation, the sensing test strip 200 is inserted into the electrochemical measuring device 100 to allow blood to flow between the working electrodes 211 and 212, and a fixed voltage is supplied from the current-voltage converting circuit 130 and the reference voltage source 120 according to the instruction of the processor 150. The voltage is between the working electrodes 211 and 212, so that a current is generated between the working electrodes 211 and 212, and the current corresponds to the blood glucose concentration in the blood. Subsequently, the current-voltage conversion circuit 130 converts the aforementioned current into a voltage, and the analog-to-digital conversion circuit 140 converts the analog value of the aforementioned voltage into a digital value, and outputs the digital value of the aforementioned voltage to the processor 150. The processor 150 calculates a blood glucose concentration based on the digital value of the aforementioned voltage, and finally displays the blood glucose concentration through the display 150.

3 is a flow chart showing a method of compensating blood glucose concentration according to an embodiment of the present invention. As shown in FIG. 3, in an embodiment of the present invention, the method for compensating blood glucose concentration can be applied to an electrochemical measuring device 100, and the method for measuring the blood glucose concentration of a blood to be measured, and compensating for the blood glucose concentration, comprises the following steps.

Step S02: preparing a plurality of sample blood, and the sample blood has a different and known hematocrit ratio and a blood glucose concentration actual value.

Step S04: respectively supplying a predetermined voltage to the sample blood, and measuring a plurality of current values during a measurement, and then measuring a plurality of blood glucose concentration measurement values according to the current values.

Step S06: determining a known hematocrit ratio by linear regression according to the known hematocrit ratio of the sample blood and the actual value of the blood glucose concentration and the blood glucose concentration measurement of the sample blood. In the case of a linear relationship between the actual value of the blood glucose concentration and the measured value of the blood glucose concentration (hereinafter referred to as the concentration linear relationship), the slope of the linear relationship of the concentrations is obtained.

In one embodiment, the Least Squares Linear Regression Analysis method is used, according to the known blood glucose concentration actual value Glu _acu (Hct) of the sample blood; and the electrochemical measuring device 100 is used. The measured blood glucose concentration measurement Glu _mea (Hct) is used to obtain a linear relationship of the aforementioned concentration in the case of a known hematocrit ratio Hct. Glu _mea (Hct)=Slope(Hct)*Glu _acu (Hct)+Re( Hct), where the slope Slope(Hct) and the remainder Re(Hct) are constant. It can also be corrected to Glu _acu (Hct)=Glu _mea (Hct)/Slope(Hct)+Re'(Hct). Figure 4 shows a linear plot of concentration of blood glucose concentration measurements and actual blood glucose concentration values at different hematocrit ratios. As shown in Fig. 4, the lines L20, L40 and L60 in Fig. 4 are the linear relationship between the actual value of blood glucose concentration and the measured value of blood glucose concentration in the case of hematocrit ratios of 20%, 40% and 60%, respectively. The slopes Slope(Hct) of the lines L20, L40, and L60 are S20, S40, and S60 (as shown in FIG. 5).

Step S08: Find at least a first relationship between the slopes and the volume ratios of the blood cells according to the slope of the concentration linear relationship and the blood cell volume ratio of the sample blood. In one embodiment, the at least one first relation is linear (hereinafter referred to as a slope linear relationship), and the least square error linear regression method is used to obtain a slope linear relationship such as Slope(Hct)=a*. Hct+b, where a and b are constants.

In one embodiment, the at least one slope linear relationship is a plurality of linear relationships. Figure 5 is a graph showing the relationship between the slope and the hematocrit ratio according to an embodiment of the present invention. In Fig. 5, S30 and S50 are the slopes of the linear relationship between the actual blood glucose concentration value and the blood glucose concentration measurement value in the case where the hematocrit ratio is 30% and 50%. As shown in FIG. 5, the line L23 represents a linear relationship between the slopes S20 and S30 and the hematocrit ratio of 20% and 30%. Line L34 represents a linear relationship between the slopes S30 and S40 and the hematocrit ratio of 30% and 40%. Line L45 represents a linear relationship between the slopes S40 and S50 and the hematocrit ratio of 40% and 50%. Line L56 represents a linear relationship between the slopes S50 and S60 and the hematocrit ratio of 50% and 60%. In an embodiment, the at least one linear relationship is only a linear relationship. As shown in FIG. 5, the line L16 represents a linear relationship between the slopes L20, L30, L40, L50, and L60 and the hematocrit ratios of 20%, 30%, 40%, 50%, and 60%.

In an embodiment, the at least one first relation is a nonlinear relationship. Figure 6 is a graph showing the relationship between the slope and the hematocrit ratio according to an embodiment of the present invention. As shown in FIG. 6, line NL16 represents a nonlinear relationship between the slopes L20, L30, L40, L50, and L60 and the hematocrit ratios of 20%, 30%, 40%, 50%, and 60%, and the aforementioned nonlinear relationship. The formula may be a multiple equation, such as Slope(Hct)=a*Hct ³ +b*Hct ² +c*Hct+d, where a, b, c, and d are constants.

Step S10: supplying a predetermined voltage to the blood to be tested through the electrodes, and generating an electrical signal to measure the blood glucose concentration measurement value of the blood to be tested according to the electrical signal.

Step S12: Calculate the blood glucose concentration compensation value of the blood to be tested according to the blood glucose concentration measurement value of the blood to be measured, the blood volume ratio of the blood to be tested, and the at least one first relational expression. There are many methods for measuring the volume ratio of blood cells, for example, a method of measuring blood impedance; an optical method; a redox reaction; and an electrochemical method to obtain a blood cell volume ratio. It should be understood that the measurement method of the hematocrit ratio of the blood to be tested is not limited in the present invention, and those having ordinary knowledge in the art can measure the hematocrit ratio of the blood to be tested according to the current or future development techniques.

In an embodiment, step S12 may include the following steps.

Step S22: Determine a measured slope corresponding to the hematocrit ratio of the blood to be tested according to the hematocrit ratio of the blood to be tested and the at least one first relational expression. As shown in FIG. 5, in the embodiment in which the at least one first relationship includes a plurality of linear relationships, when the blood volume ratio measured by the electrochemical measuring device 100 of the blood to be measured is n% and n% When between 20% and 30%, the line L23 corresponding to the hematocrit ratio n% is selected, and the measured slope Slope(n) can be obtained according to the linear relationship between the hematocrit ratio n% and the slope L23. In the embodiment in which the at least one first relationship includes only one linear relationship, the measured slope Slope(n) can be obtained directly according to the linear relationship between the blood cell volume ratio n% and the slope L16. In the embodiment in which the at least one first relation includes a nonlinear relationship, the measured slope Slope(n) can be obtained directly according to the hematocrit ratio n% and the nonlinear relationship represented by the line NL16.

Step S24: determining a compensation relationship Glu _com (n)=Glu _mea (n)/Slope(n)+Re'(n) when the hematocrit ratio is n% according to the measured slope Slope(n), and The blood glucose concentration measurement value of the blood to be measured is compensated according to the aforementioned compensation relationship to obtain a blood sugar concentration compensation value. In the present embodiment, the aforementioned compensation relationship is linear, as shown in FIG. 4, and the linear relationship of the concentration when n% is represented by the line Ln in FIG. 4 Glu _mea (n)=Slope(n)*Glu _com (n ) +Re(n). According to the compensation relationship, the blood glucose concentration when the hematocrit ratio is n% can be compensated to the blood glucose concentration when the blood cell volume ratio is a standard value (about 40%).

In one embodiment, an experiment may be performed using a plurality of sample blood to obtain the linear relationship of the concentration and the linear relationship of the slope, and stored in the memory 170 of the electrochemical measuring device 100. After measuring the blood volume ratio of the blood to be tested and the blood glucose concentration measurement value, the blood glucose concentration measurement value of the blood to be measured is compensated.

Fig. 7A is a graph showing the relationship between the blood glucose concentration and the amount of deviation when blood glucose concentration compensation is not performed. Fig. 7B is a graph showing the relationship between the blood glucose concentration and the amount of deviation when the blood glucose concentration is compensated. As shown in FIG. 7A and FIG. 7B, the deviation amount of the blood glucose concentration is significantly reduced when the blood glucose concentration is compensated by the method for compensating the blood glucose concentration according to an embodiment of the present invention.

In the conventional technique, a large number of experiments are required to make a data table, and when the blood glucose concentration measurement value is compensated, a large number of selection operations are required, and the corresponding data group is found from the data table, and finally the blood sugar is performed. Compensation for concentration. However, the data table requires a large storage capacity, and a large number of selection operations require a more powerful processor. Although the above data table can be easily stored or selected in a general computer, the use of a blood glucose machine to store the aforementioned data table or perform a group selection operation requires additional cost.

In contrast, according to an embodiment of the present invention, the memory 170 only needs to store a plurality of sets of equations, and the storage capacity used is small, and does not require a large number of selection operations, even in the foregoing at least one first relationship. In one embodiment, the selection operation is not required, so that the computational load of the processor of the electrochemical measuring device 100 can be reduced, and the electrochemical measuring device 100 can operate smoothly, without requiring too much time for calculation.

While the present invention has been described in its preferred embodiments, the present invention is not intended to limit the invention, and the present invention may be modified and modified without departing from the spirit and scope of the invention. The scope of protection is subject to the definition of the scope of the patent application. In addition, any of the objects or advantages or features of the present invention are not required to be achieved by any embodiment or application of the invention. In addition, the abstract sections and headings are only used to assist in the search of patent documents and are not intended to limit the scope of the invention.

100. . . Electrochemical measuring device

111. . . Connection

112. . . Connection

120. . . Reference voltage source

130. . . Current-voltage conversion circuit

140. . . Analog digital conversion circuit

150. . . processor

160. . . monitor

170. . . Memory

200. . . Sense test piece

211. . . Working electrode

212. . . Working electrode

Figure 1 is a graph showing the relationship between the measured value of blood glucose concentration measured by a conventional blood glucose meter and the actual value of blood glucose concentration at different hematocrit ratios.

2 is a functional block diagram of an electrochemical measuring device in accordance with an embodiment of the present invention.

3 is a flow chart showing a method of compensating blood glucose concentration according to an embodiment of the present invention.

Figure 4 shows a linear plot of concentration of blood glucose concentration measurements and actual blood glucose concentration values at different hematocrit ratios.

Figure 5 is a graph showing the relationship between the slope and the hematocrit ratio according to an embodiment of the present invention.

Figure 6 is a graph showing the relationship between the slope and the hematocrit ratio according to an embodiment of the present invention.

Fig. 7A is a graph showing the relationship between the blood glucose concentration and the amount of deviation when blood glucose concentration compensation is not performed.

Fig. 7B is a graph showing the relationship between the blood glucose concentration and the amount of deviation when the blood glucose concentration is compensated.

Claims (10)

A method for compensating blood glucose concentration, which uses a sensing test piece including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece to measure a blood glucose concentration compensation value of a blood to be measured between the electrodes The method for compensating blood glucose concentration comprises: using a plurality of sample blood having different and known hematocrit ratios and actual blood glucose concentration values, measuring blood glucose concentration values of the blood samples, and obtaining the blood samples. a slope between the actual value of the blood glucose concentration and the measured value of the blood glucose concentration, and determining at least a first relationship based on the ratio between the actual value of the blood glucose concentration of the sample blood and the measured value of the blood glucose concentration and the volume ratio of the blood cells Supplying a predetermined voltage to the blood to be tested through the electrodes, generating an electrical signal to measure a blood glucose concentration measurement value of the blood to be tested according to the electrical signal; and a blood cell volume ratio according to the blood to be tested and the At least a first relationship, determining a measured slope between the actual blood glucose concentration value and the blood glucose concentration measurement value of the blood to be tested, and according to the blood glucose concentration of the blood to be tested Measured value and the measured slope value calculated by the compensation of the blood glucose concentration of the blood test. The method of compensating blood glucose concentration according to claim 1, wherein the at least one first relationship is a plurality of linear relationships. The method for compensating blood glucose concentration according to claim 2, wherein the calculating the blood glucose concentration compensation value of the blood to be tested comprises: according to the blood volume ratio of the blood to be tested, from the first relationship Wherein the first relational expression corresponding to the hematocrit ratio of the blood to be tested is selected; and the blood glucose ratio of the blood to be tested is determined according to the hematocrit ratio of the blood to be tested and the selected first relationship The measured slope between the actual concentration value and the blood glucose concentration measurement value, and the blood glucose concentration compensation value of the blood to be tested is calculated according to the blood sugar concentration measurement value of the blood to be tested and the measured slope. The method of compensating blood glucose concentration according to claim 1, wherein the at least one first relationship comprises only a linear relationship. The method of compensating blood glucose concentration according to claim 1, wherein the step of obtaining at least a first relationship comprises: preparing the samples having different and known hematocrit ratios and blood glucose concentration actual values. Blood, and measuring the blood glucose concentration measurement values of the blood of the samples; according to the known blood volume ratio of the sample blood and the actual value of the blood glucose concentration, and the blood glucose concentration measurement values of the sample blood, using linear regression method, respectively Obtaining a blood glucose concentration ratio between the actual blood glucose concentration and the blood glucose concentration measurement value of a known blood cell volume ratio a second relationship, wherein the second relationship is linear and the slopes of the second relationships are the actual value of the blood glucose concentration of the sample blood and the slope of the blood glucose concentration measurement; according to the second relationship The slope of the formula and the hematocrit ratio of the blood of the samples are used to determine the at least one first relationship. The method for compensating blood glucose concentration according to claim 5, wherein the calculating the blood glucose concentration compensation value of the blood to be tested comprises: determining a blood volume ratio of the blood to be tested according to the measured slope The following compensation relationship is performed, and the blood glucose concentration measurement value of the blood to be tested is compensated according to the compensation linear relationship to obtain the blood sugar concentration compensation value of the blood to be tested. A method for compensating blood glucose concentration, which uses a sensing test piece including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece to measure a blood glucose concentration compensation value of a blood to be measured between the electrodes The method for compensating blood glucose concentration comprises: preparing a plurality of sample blood having different and known hematocrit ratios and actual blood glucose concentration values, and measuring blood glucose concentration measurements of the sample blood; according to the sample blood The known hematocrit ratio and the actual value of the blood glucose concentration, and the blood glucose concentration measurement values of the blood of the samples are determined by a linear regression method to obtain a known blood cell volume ratio. a second relationship between the blood glucose concentration actual value and the blood glucose concentration measurement value, wherein the second relationship is linear; according to the slope of the second relationship and the blood cell volume ratio of the sample blood Obtaining at least a first relationship; supplying a predetermined voltage to the blood to be tested through the electrodes, generating an electrical signal to measure a blood glucose concentration measurement value of the blood to be tested according to the electrical signal; and according to the blood to be tested a blood cell volume ratio and the at least one first relationship, obtaining a measured slope between the blood glucose concentration actual value and the blood glucose concentration measurement value of the blood to be tested, and according to the blood glucose concentration measurement value of the blood to be tested and The measured slope is used to calculate the blood glucose concentration compensation value of the blood to be tested. The method for compensating blood glucose concentration according to claim 7, wherein the at least one first relationship is a plurality of linear relationships. The method for compensating blood glucose concentration according to claim 7, wherein the calculating the blood glucose concentration compensation value of the blood to be tested comprises: according to the blood cell volume ratio of the blood to be tested, from the first relationship Selecting a first relationship corresponding to a blood cell volume ratio of the blood to be tested; and determining a blood glucose concentration of the blood to be tested according to the blood volume ratio of the blood to be tested and the selected first relationship The measured slope between the value and the blood glucose concentration measurement, and based on the blood glucose of the blood to be tested The concentration measurement value and the measured slope determine the blood glucose concentration compensation value of the blood to be tested. The method of compensating blood glucose concentration according to claim 7, wherein the at least one first relationship comprises only a linear relationship.