JPS6348018B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention involves injecting sample blood or a standard solution (hereinafter referred to as sample blood, etc.) into a reaction cell comprising an immobilized enzyme membrane and a measurement electrode, and then A blood glucose analyzer that causes a chemical reaction with an immobilized enzyme membrane and measures the blood glucose concentration value of sample blood, etc. from the reaction current generated on the measurement electrode based on the chemical reaction, especially such a blood glucose analyzer. The present invention relates to a method for detecting the end point of the reaction (also referred to as reaction equilibrium time) in a blood sugar analyzer.

FIG. 1 is a block diagram of this type of blood sugar analyzer.

In FIG. 1, a glucose measuring electrode or sensor 1 that measures a reaction current proportional to a blood glucose concentration value is composed of a glycose oxidase membrane in close contact with the surface of a platinum and silver electrode. , is set in cell CE.
The buffer solution 4 is sucked by the liquid pump 3 and
The liquid is sent to the CE to clean the inside of the cell CE, and after the reaction is discarded as waste liquid 5. air pump 6
The sample blood, etc. injected into the reaction cell CE from the injection port OP is stirred by vibrating the silicon diaphragm SD to make the concentration in the cell CE uniform. A temperature sensor 7 detects the temperature of the cell block, and a heater 8 heats the cell block to the same temperature as human body temperature (for example, 37° C.). Therefore, the sample blood etc. injected into the cell CE,
It is maintained at the same temperature as the human body.

The control device CC, which mainly consists of a microcomputer CPU, is connected to the blood glucose analyzer GU via lines _L1 to _L6 , reads the reaction current from the measurement electrode 1 via line _L1 , and reads the reaction current from measurement electrode 1 via line _L2 . Read the temperature correction amount for the measured value through the line
measuring and controlling the temperature of the cell block via lines L ₄ and L ₅ and controlling the operation of the liquid pump 3 and air pump 6 via lines L ₃ and L ₆ ;
Various switches MO 1 to ₁ by line L ₇ to L ₁₁
It is connected to MO ₄ , DS ₁ to DS ₂ , display DI, and printer P, and controls the entire device, including input/output control of these. In addition, DS ₁ is the sample number setting switch, DS ₂ is the standard solution value setting switch, CAL and
RUN is a mode indicator representing calibration and operating status, respectively, and MO ₁ to MO ₄ represent these modes and mode setting switches for paper feed of printer P, setting of DS ₁ , etc.

In this type of blood sugar analyzer, the main steps are warm-up → standby → cell cleaning, sample injection →
Various operations, measurements, etc. are performed while changing the state of the device, such as from reaction to cell cleaning. The main function in each of these states is "warming".
In "Standby", the sensor part heats up, "Standby" indicates measurement READY (measurement preparation) or waiting for measurement command,
"Washing" involves cleaning the sensor section with a buffer solution, "Injection" involves injecting a blood sample or detecting the reaction starting point and transitioning to the next reaction state, and "Reaction" involves converting and displaying the glycose concentration. In each of these states or processes, various lamps are displayed or blinked to indicate the status to the operator. Therefore, in order to transition each state of the analyzer from one state to the next, it is necessary to detect and judge the transition conditions in each state.

In particular, in order to convert and obtain a blood sugar concentration value from a reaction current, accurate measurements cannot be made unless it is accurately detected at what point the chemical reaction reaches an equilibrium state or ends.

By the way, conventionally, this type of detection method uses the start-up point of the reaction as a reference point, and performs time-limited monitoring by determining a certain amount of time from this point.In other words, it is assumed that the reaction will reach equilibrium or end after a specified amount of time has elapsed. The system relied solely on monitoring during that time.

However, it has been pointed out that the immobilized enzyme membrane used in the above-mentioned blood sugar analyzer has the disadvantage that it deteriorates quickly, that is, its ability to decompose blood sugar quickly decreases, and that this slows down the change in reaction current.

FIG. 2 is a sensor output characteristic diagram for explaining such a situation.

In the same figure, a shows a sensor output characteristic diagram using a sensor with a quick response, and b shows that of a deteriorated sensor. As is clear from the figure, in the case of a fast-responsive sensor, the curve SO ₁ rises steeply from the injection point I of sample blood, etc., whereas when the sensor deteriorates, it curves gently as shown by SO _2. It becomes a curve. Therefore, if the sensor has deteriorated, it is not possible to detect whether the reaction is saturated, terminated, or in progress by simply monitoring the predetermined time _T1 , and it is difficult to accurately determine the amount of reaction. It becomes possible. Conversely, in the case of a sensor that responds quickly, even though it reaches saturation or termination state in a short time,
Measurement will not be performed until the predetermined time _T1 has elapsed, and this time will be wasted, and the processing capacity of the blood glucose meter will therefore be reduced.

This invention was made in view of the above, and aims to eliminate the above-mentioned drawbacks and enable highly accurate measurements by easily and accurately detecting the end of a reaction. It is something to do.

The feature of this invention is that the output of the immobilized enzyme membrane sensor in the blood sugar analyzer is sampled at regular time intervals and sequentially stored in the memory, and the series of stored data is divided into new and old data according to the order of sampling. Calculate the average value of each group, calculate the difference between them, and when the difference becomes less than a predetermined value, the reaction is considered to have ended.
The point is that the end point of the reaction can be detected using the newest data among the data stored at that time.

Embodiments of the present invention will be described below with reference to the drawings.

FIG. 3 is a block diagram showing an embodiment of the invention, FIG. 4 is an explanatory diagram for explaining the detection method according to the invention, and FIG. 5 is a flowchart showing the measurement operation according to the invention.

In FIG. 3, the output of the glucose measuring electrode or sensor is applied to a differential amplifier 21 and the A/D
The signal is supplied via a converter 22 and a buffer 23 to a microcomputer CPU constituting a control device.
Note that RAM is random access memory.

Here, when sample blood or the like is injected into the reaction cell, a reaction current is generated in the glycose measuring electrode or sensor based on a chemical reaction. This reaction current is
The signal is amplified by the differential amplifier 21 and converted into a voltage signal, and further converted into a digital signal by the A/D converter 22 and sent to the microcomputer.
Given to CPU. microcomputer cpu
samples the sensor output at predetermined time intervals from the time of sample injection (when the washing is completed and enters the injection mode), and stores the sampling data at each time point in a predetermined area DR of the RAM. Here, if six pieces of sampling data, such as D ₆ to D ₁ , are arranged in the RAM area DR in the oldest order, the microcomputer CPU stores these six data points D ₁ to _{D 6} as two sets of three D _A , D ₁ , D ₂ , D ₃ and D _B , D ₄ , D ₅ , D ₆ , that is, if we divide them into two sets, a new data set and an old data set, and calculate the average value of each. , calculate these differences. These differences are considered to represent the change in the current measured value from the previous value, and if this value becomes small, it can be assumed that the chemical reaction is saturated. When the difference becomes less than a predetermined value, for example, 1 mg/dl, the reaction is detected to have ended. If the difference does not become less than the predetermined value, remove the oldest data D ₆ from area DR, put the newest data D ₀ there, and add the old data group consisting of D ₅ to _{D 3} and D ₂ Between the new data group consisting of ~D ₀ ,
The same process as above is performed again. Such processing is
This process is repeated until the difference between the average values of the new data group and the old data group becomes equal to or less than a predetermined value. Thereafter, when the difference becomes less than or equal to a predetermined value, the point where the latest data used at that time was obtained is detected as the reaction end point. In addition, in the above, whether the difference between each average value is positive or negative, the reaction is considered to be completed when it becomes equal to or less than a predetermined value.

The above process is a type of so-called digital differential operation that calculates the difference between sample values at arbitrary two points. This allows for more stable detection than when detecting points one by one.

FIG. 4 shows the relationship between sensor output and sampling data. Here, for sensor output S ₀ , time
An example is shown in which six pieces of data _D6 to _D1 are sampled during _T2 .

When the end of the reaction is detected in this way, the sensor output at this time is converted into a blood glucose concentration value and displayed, but as explained earlier, the enzyme membrane sensor deteriorates and does not respond. It is possible that the reaction may be delayed and it may take some time to detect the end of the reaction, so in this case, monitor for a certain period of time as shown in Figure 5, and when the predetermined period of time has elapsed, the measurement is complete. and transitions to the next state.

Note that in the above example, six pieces of sampled data are stored in the random access memory, but it is clear that the number of data to be employed or the type of memory is not limited to the above.

Furthermore, although a blood glucose analyzer has been described above, the present invention can be widely applied to general analysis or measurement devices equipped with an enzyme membrane sensor consisting of an immobilized enzyme membrane and a measurement electrode.

This invention provides the advantage that the end of the reaction is easily and accurately detected, thereby significantly increasing the throughput of the blood glucose meter.

[Brief explanation of the drawing]

FIG. 1 is a block diagram showing the overall configuration of the blood glucose analyzer, FIG. 2 is an explanatory diagram comparing and explaining cases where the output characteristics of the sensors are different, and FIG. 3 is a block diagram showing an embodiment of the present invention. FIG. 4 is an explanatory diagram for explaining the detection method according to the present invention, and FIG. 5 is a flow chart showing the measurement operation according to the present invention. Explanation of symbols 1...Glucose measurement electrode or sensor, 21...Differential amplifier, 22...A/D converter, 2
3...Buffer, CPU...Microcomputer,
RAM...random access memory, CE...reaction cell, OP...inlet, GU...analyzer.

Claims (1)

[Claims] 1 A chemical reaction is caused by injecting sample blood into a reaction cell equipped with an enzyme membrane sensor consisting of an immobilized enzyme membrane and a measurement electrode, and the reaction current generated in the sensor based on the chemical reaction is used to detect the sample blood. A method for detecting the end point of the reaction in a blood sugar analyzer configured to measure blood glucose concentration, the method comprising: sampling the sensor output at regular time intervals; and sequentially storing the obtained sampling data in a memory; Initially, when the number of data reaches a predetermined number, it is divided into old data groups and new data groups of the same number in the sampling order, and the average value and difference between them are calculated. From then on, every time new data is sampled, Discard the oldest data in the data group, move the oldest data in the new data group to the old data group, and add the newly sampled latest data as data in the new data group, and do the same as above. A method for detecting the end point of a reaction, characterized in that when the difference exceeds a predetermined value, the point at which the latest data is obtained among the data is detected as the end point of the reaction.