JPH0778480B2 - Method for automatic calibration of solute concentration measuring electrode in solution - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for automatically calibrating an electrode for measuring a solute concentration in a solution, and particularly to an electrode for measuring blood glucose, which is important in the medical field. Regarding automatic calibration method.

[Prior art and its problems]

Measuring the blood glucose level (glucose concentration in blood) and automatically injecting insulin when treating a diabetic patient is a well-known technique in the medical field as already seen in many documents. Further, in order to perform this series of operations, a blood glucose level measuring electrode for measuring the blood glucose level of the patient and an insulin infusion for calculating an injecting amount of insulin suitable for each patient based on the blood glucose level according to a predetermined calculation formula. An artificial pancreas composed of an amount determining means and an insulin injecting means for injecting the amount of insulin determined by this means into a patient is also well known. The basic operation of such a series of operations is the measurement of the blood glucose level of each patient, and the error in the measurement value may even reach the amount of insulin infused and pose a serious risk to the patient. Therefore, for example, when using the artificial pancreas, it is important to internally calibrate the blood glucose measurement electrode immediately before use to minimize the blood glucose measurement error. For this reason, in each hospital that uses an artificial pancreas, the doctor or technician in charge starts calibration immediately after going to work in the morning to calibrate the electrodes for measuring blood glucose level, and manually performs the calibration procedure over a considerable period of time. It is the actual situation. However, since this manual calibration procedure requires the judgment of the electrode stable state and the dial setting operation by a human being, it requires a considerable skill depending on the human feeling, and sometimes the judgment is erroneous, leading to an inaccurate measurement. Sometimes. As described above, the calibration of the blood glucose measurement electrode is unavoidable in spite of the considerable labor of the doctor in charge, but sometimes it is inaccurate.

[Problems to be solved by the invention]

By eliminating the conventional drawbacks associated with the calibration of blood glucose measurement electrodes as described above, and activating the calibration switch by the technician or the timer before attending the attending doctor, all calibration procedures are performed automatically, and There is a demand for a safe and simple method for calibrating the blood glucose measurement electrode, which can avoid the inaccuracy of the measuring instrument and the malfunction of the artificial pancreas due to the error of the judgment and operation of the above. As described above, such a proofreading method can significantly reduce the burden on the doctor in charge, and thus contributes greatly to the medical field.

Therefore, an object of the present invention is to perform automatic calibration of a measurement electrode that can automatically perform internal calibration and external calibration, respectively, of an electrode that measures a solute concentration in a solution such as a blood glucose measurement electrode that has been manually performed conventionally. To provide a method.

[Means for solving problems]

In order to achieve the above-mentioned object, in the present invention, the base solution and the calibration solution each having a target solute concentration of zero are set in respective containers, and the base solution is caused to flow to the measurement electrode by operating an internal calibration start switch. The electrode output value (iB) and the electrode output change rate (ΔiB / min) at the time of passing are respectively detected, and the progress of the electrode output change rate is judged based on the value of the electrode output change rate. The value (iB) is stored, and if the progress is not detected, the detection of the electrode output change rate is continued, and then the base solution is automatically switched to the calibration solution by a signal indicating that the progress is possible, and the calibration solution is measured. The electrode output value (iS) at the time of passing through was detected, and the difference (iS-iB) from the electrode output value (iB) at the time of passing the base liquid over the measuring electrode was calculated. A method for measuring the concentration of solute in a solution, which is characterized by judging whether or not to proceed to the next step. To provide an automatic calibration of the method.

In the above automatic calibration method, it is preferable to set all the operations to be automatically repeated at least twice.

In addition, it is preferable to set the magnitude of the electrode output value (iB) as a judgment factor when judging whether or not to proceed to the next step by passing the base liquid over the measurement electrode.

Further, in the above-mentioned automatic calibration method, an electrode output value (iS) when the calibration liquid is passed over the measurement electrode and an electrode output value (iB) when the base liquid is passed over the measurement electrode When the difference (iS-iB) value of the standard is ready to proceed to the next step, insert the solution sampling port into the standard solution and operate the external calibration start switch to flow the standard solution to the measurement electrode. The electrode output value (I) at the time of the passage is detected, and the relationship between the solute concentration and the electrode output value is determined from this and the electrode output value (iB) at the time when the base liquid is passed over the measurement electrode. By doing
External calibration can be done automatically.

Furthermore, in the above-mentioned automatic calibration method, the solution is blood, the solute is glucose, and the liquid sampling port is a catheter having a blood diluting function, which is effectively applied as an automatic calibration method of the blood glucose measurement electrode. You can

[Action]

When the automatic calibration method of the present invention having the above-mentioned configuration is applied to a blood glucose measurement electrode, for example, not only can internal and external calibration operations be performed automatically, but the electrode output value obtained in internal calibration can also be obtained. The level of the difference (iS-iB) in (voltage value or current value) can be selectively set within a predetermined range according to the solute concentration (sugar concentration) of the calibration solution, so the actual solute concentration (blood glucose level) This range is convenient because the range can be appropriately expanded or reduced to suit the accuracy of the solute concentration measurement value (blood glucose measurement value) and the continuous use time.

In the automatic calibration method of the present invention, the electrode output change rate (ΔiB / min) is the change in the electrode output value (voltage value or current value) after a certain period of time divided by time, and in this case, the time Is preferably 1 to 5 minutes.

The small change rate of the electrode output indicates that the measurement electrode is stable.

In addition, the output value of the measuring electrode may decrease or increase uniformly depending on the type of the measuring electrode when the liquid starts to flow, and may converge to a constant value. Therefore, in the enzyme electrode for measuring blood glucose, when the base solution is passed through, it initially shows a relatively large value, then shows a uniform decreasing tendency, and converges to zero. In this case, if the electrode is stable, the rate of change of the electrode output value becomes small and the output value itself becomes sufficiently close to the convergence value. Therefore, it is also a preferred embodiment to use the magnitude of the electrode output value (iB) together with the magnitude of the electrode output change rate (ΔiB / min) to determine whether or not to proceed to the next step. As a result, when the electrode output value becomes stable at an abnormal value, it is possible to prevent the process from proceeding to the next step and prevent abnormal measurement due to the progress.

In addition, the difference in the electrode output value (voltage value or current value) (iS
Whether or not to proceed to the next step based on the value of -iB) is determined by comparison with the set value determined by the sensitivity of the electrode, the concentration of the calibration solution used and the target measurement accuracy.

Note that, in general, the calibration of the measurement electrode usually repeats a predetermined calibration procedure twice or more for the sake of accuracy, and therefore the significance of performing all these calibration operations automatically becomes even greater. . Also, when the internal calibration is performed twice or more, the final electrode output value is stored, but it is necessary to store each electrode output value and use the average value of them. You can also

When calibrating the measurement electrode, it is common to use a solution with a concentration of the solute to be measured of 0 as the base solution, and when diluting blood to measure the blood glucose level, use the diluted solution as the base solution. Preferably. Further, as the calibration solution, a solution having a sugar concentration having a predetermined value within a range of 2 to 10 mg / dl, particularly a sugar concentration of about 6 mg / dl is suitable.

According to the present invention, when performing the automatic calibration method of the blood glucose measurement electrode, the current value (iB) of the electrode output when the base solution is passed through is 2.5 nA (where nA is nanoampere, that is, 10 A).
^-9 A is shown below) and the electrode output change rate (ΔiB
/ min) is 0.06nA / 3min or less, and the difference (iS-iB) between the current value (iS) and the current value (iB) when a calibration solution having a sugar concentration of 6 mg / dl is passed through It is preferable to set it to 6.0 nA or more.

In addition, when measuring the blood glucose level of diabetic patients, it is generally 50-90.
The measurement of a blood glucose level of 0 mg / dl becomes a problem. To measure such a level, dilute the concentration in the device with a diluting solution (or a base solution), and use the calibration method of the present invention to set the electrode Of course, it can be determined by extrapolation after point calibration.

〔The invention's effect〕

According to the present invention, when the base solution and the calibration solution each having a target solute concentration of zero are set in respective containers, and the base solution is passed through the measurement electrode by operating the internal calibration start switch automatically or manually. The electrode output value (iB) and the electrode output change rate (ΔiB / min) are respectively detected, and it is judged whether or not the electrode output change rate can proceed to the next process. If the progress is not detected, the detection of the electrode output change rate is continued, and then the base solution is automatically switched to the calibration solution by the signal indicating that the progress is possible, and the calibration solution is passed over the measurement electrode. Electrode output value (i
S) is detected and by calculating the difference (iS-iB) from the electrode output value (iB) when the base liquid is passed over the measurement electrode and determining whether or not to proceed to the next step, Internal calibration of the solute concentration measuring electrode can be automatically performed.

Then, the difference (iS-) between the electrode output value (iS) when the calibration solution is passed over the measurement electrode and the electrode output value (iB) when the base solution is passed over the measurement electrode. When the value of iB) can proceed to the next step, put the liquid sample sampling port into the standard solution and operate the external calibration start switch automatically or manually to allow the standard solution to flow over the measuring electrode. The electrode output value (I) at the time of application is detected, and the relationship between the solute concentration and the electrode output value is determined from this and the electrode output value (iB) at the time when the base liquid is passed over the measurement electrode. By
External calibration of the solute concentration measurement electrode can be automatically performed.

In this way, according to the present invention, it is possible to accurately, safely and simply achieve the initial internal calibration and external calibration of the measurement electrode, which has conventionally been manually burdened with a great burden.

〔Example〕

An automatic calibration method for a blood glucose measurement electrode applied to an artificial pancreas will be described below as an embodiment of the automatic calibration method according to the present invention with reference to the accompanying drawings.

FIG. 1 is an operation flow chart showing an automatic calibration method according to the present invention, in which only the operation shown as “manual” in the drawing is performed by a medical doctor or a technician, and the remaining operation is automatically performed by a microcomputer incorporated in the artificial pancreas. It will be clear from the drawings that what is done is done.

First, the initial internal calibration is started in consideration of the time required for the calibration, and at that time, the person in charge only needs to manually activate the internal calibration switch. After that, aspirate the base liquid →
Check the electrode stability → Check and store the electrode output value and electrode output change rate with the base solution → Suction of calibration solution → Confirm the electrode output stability → Check and store the electrode output value with the calibration solution Do it automatically. In the conventional calibration operation, the confirmation of the electrode stability is performed by human judgment, which requires skill and a considerable feeling, and sometimes the confirmation judgment is erroneous and the measurement accuracy of the electrode deteriorates. In addition, it was necessary to manually rotate the adjustment knob after checking the electrode stability to match the zero point and the scale of the specified value with the calibration liquid, so this operation requires skill and feeling, which is bothersome and inaccurate. Met.

Then, the fully automatic operation procedure by the microcomputer is automatically repeated once again to improve the measurement accuracy. As a result of repeating the calibration procedure twice or more for the same purpose even in the conventional manual operation, the inaccuracy depending on the judgment and the feeling of the human being described above is expanded or the trouble is doubled.

Generally, in the calibration procedure of the measuring electrode, it is usual to perform external calibration after internal calibration. In the external calibration procedure of the present invention, the catheter is manually placed in the standard solution and the external calibration solution switch is activated. This operation is a simple operation that requires neither judgment nor feeling. After that,
The microcomputer automatically performs a calibration procedure consisting of confirmation of electrode output stability, and then checking and storing the output value of the external calibration liquid. Incidentally, in the conventional external calibration procedure, since all of these operations were performed manually, the burden on the person in charge and inaccuracy were unavoidable for the same reason as above.

According to the present invention, for example, a base solution having a sugar concentration of zero and a calibration solution having a sugar concentration of 6 mg / dl are set in a container in the apparatus, and the electrode output current value (iB) and The electrode output change rate (ΔiB / min) and the difference in electrode output current value (iS-iB) when switching to the calibration solution are 2.5n each.
Simply set to A, 0.06nA / 3min and 6.0nA, and after that, the internal calibration is automatically repeated only by activating the switch, and then the external calibration is also performed by dipping the catheter in the standard solution. Only a simple operation with the switch energizing is performed, and thereafter the operation is automatically performed by the microcomputer. Thus, the automatic calibration method according to the present invention is safe, accurate, and simple, and greatly contributes to the medical field in that the calibration method for blood glucose measurement electrodes, which has been a difficult point in the related art, is significantly improved.

Next, a flow chart of FIGS. 2- (1), (2), (3) and (5) and an internal calibration time chart diagram of FIG. 2- (4) regarding the operating principle of the blood glucose level measuring electrode according to the present invention. A description will be given below with reference to FIG.

The flow of the liquid in the measurement chamber is shown in Fig. 2- (1) or the flow of the liquid in the injection system is shown in Fig. 2- (2).

During the "operation" process, a small amount of blood is continuously collected from the patient by the multi-channel pump 10 via the catheter 12 and the blood collection tube, and first the primary dilution (about 5 times) is performed with the heparinized physiological saline solution 14, and then the diluted solution. Second dilution (about 7 times) is performed to dilute the blood in two steps, mix in the collecting pipe 16, pass through the bubble removal pipe 18, and then warm to an appropriate temperature and lead to the oxygen electrode 20 for blood sugar. After continuously measuring the values, the waste liquid is discharged to the waste liquid bottle 22. Note that reference numeral 15 indicates a liquid dead detector.

Insulin and glucose infusion amounts are calculated from the obtained blood glucose level by a predetermined arithmetic control formula, and the insulin and glucose are infused into the patient from the insulin solution container 26 and the glucose solution container 28 via the insulin pump 32 and the glucose pump 34, respectively. (See FIG. 2- (2)).

Since the flow changes depending on each process, these will be described below.

(1) Internal calibration The oxygen electrode 20 was supplied with a diluting solution (RS-D3) having a sugar concentration of 0 mg / dl and an electrode calibrating solution (RS-C3) having a constant sugar concentration as the base solution alternately twice. The output current value of the enzyme electrode 20 for the liquid is stored.

The flow is divided into two types: diluent and electrode calibration solution [No. 2-
(3)] The solenoid valves 40 and 42 are automatically switched to switch the liquid flow.

The output current for each liquid is as shown in Fig. 2- (4),
The output current value is displayed on the blood glucose display, and the graph and the value are printed on the printer. After this step, each solution is automatically flowed every hour for calibration.

(2) External calibration After the internal calibration is completed, the glucose standard solution (RS-G200) having a sugar concentration of 200 mg / dl is sucked from the catheter 12 having a blood diluting function to store the output current value (I) of the enzyme electrode (20). To do.
The relationship between the glucose concentration and the output current of the enzyme electrode 20 can be known from the output current value of the diluent and the output current value (I) of the glucose standard solution stored in the “internal calibration” step. After that, the blood glucose level is obtained from the output current in the "measurement" step.

This flow is shown in Fig. 2- (5). After completing external calibration,
The diluent flows [Fig. 2- (3) (a)]. All calibration is done automatically.

(3) Measurement The patient's blood is sucked from the catheter 12 and the blood glucose level is continuously measured by the enzyme electrode 20. The flow is the same as the "external calibration" step [Fig. 2- (5)].

(4) Driving The blood glucose level of the patient is continuously measured, and the insulin solution or glucose solution is injected into the patient according to a predetermined calculation control formula based on the obtained value to control the blood glucose. The flow is the same as in the "external calibration" step [Fig. 2- (5)].

An embodiment of the automatic electrode calibration method according to the present invention according to the above operation principle is shown in a graph in FIG. In FIG.
The internal calibration (initial) serves as the internal calibration standard after the start of measurement, and the external calibration serves as the initial sugar concentration standard. Third
The computer stores the circles shown in the graph of the figure.
Each numerical value shown in FIG. 3 is calculated according to the following equation.

Therefore, 14.70 + 1.12 = 15.82 (nA) 14.70 (nA) corresponds to glucose 200 mg / dl.

As is apparent from the above-mentioned embodiments, according to the present invention,
In the internal calibration performed first, it is possible to easily confirm that the electrode itself is normal by calibrating the measurement electrode in the flow path that does not include the catheter or the multi-channel pump. Next, in the external calibration performed subsequent to the internal calibration, the measurement electrode is calibrated in a state where the catheter and the multi-channel pump are included in the flow path, so that the catheter and the multi-channel pump in the actual electrode measurement are included. It is possible to reliably and easily confirm the quality of the flow path or the safety.

Although the present invention has been described above with reference to internal calibration and external calibration of blood glucose measurement electrodes using, for example, an artificial pancreas, the basic idea of the present invention can be applied to automatic calibration of electrodes across all automated medical devices such as glucose monitors. Of course.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an operation flow chart for explaining the operation of the automatic calibration method for a blood glucose measurement electrode according to the present invention, and FIGS. 2- (1) to 2- (5) are blood glucose according to the present invention. FIG. 3 is a flow chart of each step showing the operating principle of value measurement and an internal calibration time chart, and FIG. 3 is a characteristic curve diagram showing one embodiment of the electrode automatic calibration method according to the present invention. 10 …… Multi-channel pump 12 …… Catheter, 14 …… Heparinized saline 15 …… Discharge detector, 16 …… Collection pipe 18 …… Bubbling pipe, 20 …… Oxygen electrode 22 …… Waste liquid bottle, 24 …… Saline solution 26 …… Insulin solution container, 28 …… Glucose solution container 30 …… Drainage detector, 32 …… Insulin pump 34 …… Glucose pump, 36 …… Bubble detector 38 …… Blood collection Detector, 40 ... Solenoid valve 42 ... Solenoid valve

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yoshihiko Izumiji 3-43-2, Ebisu, Shibuya-ku, Tokyo Within Nikkiso Co., Ltd. (72) Inventor Arihiro Nanba 3-43-2, Ebisu, Shibuya-ku, Tokyo Nikkiso Co., Ltd.

Claims (5)

[Claims] 1. An electrode output when a base solution and a calibration solution each having a target solute concentration of zero are set in respective containers, and the base solution is passed through the measurement electrode by operating an internal calibration start switch. The value (iB) and the electrode output change rate (ΔiB / min) are respectively detected, and whether or not the electrode output change rate can proceed to the next process is judged. If the progress is possible, the electrode output value (iB) is stored. If the progress of the electrode is not detected, the detection of the electrode output change rate is continued, and then the base solution is automatically switched to the calibration solution by a signal indicating that the progress is possible, and the calibration solution is passed over the measurement electrode. The electrode output value (iS) of the electrode is detected and the electrode output value (i
A method for automatically calibrating a solute concentration measuring electrode in a solution, which comprises calculating a difference (iS-iB) from B) and determining whether or not to proceed to the next step. 2. The difference (iS) between the electrode output value (iS) when the calibration liquid is passed over the measuring electrode and the electrode output value (iB) when the base liquid is passed over the measuring electrode. -When the value of (iB) is ready for the next step, the solution sampling hole is put into the standard solution, and the standard solution is passed through the measurement electrode by operating the external calibration start switch. By detecting the electrode output value (I) of the electrode and determining the relationship between the solute concentration and the electrode output value from this and the electrode output value (iB) when the base liquid is passed over the measuring electrode. A method for automatically calibrating an electrode for measuring a solute concentration in a solution according to claim 1, wherein the electrode is calibrated. 3. The electrode output value (iB) when judging whether or not to proceed to the next step by passing the base liquid through the measuring electrode.
The method for automatically calibrating an electrode for measuring a solute concentration in a solution according to claim 1, wherein the size of is also used as a criterion. 4. An automatic calibration method for a solute concentration measuring electrode in a solution, wherein all the operations in the automatic calibration method according to claim 1 are automatically repeated at least twice. 5. The automatic calibration method for a blood glucose measuring apparatus according to claim 2, wherein the solution is blood, the solute is glucose, and the liquid sampling port is a catheter having a blood diluting function.