JP4985340B2 - Biosensor system and measuring instrument - Google Patents

Description

  The present invention relates to a biosensor system for measuring biological information of a biological material supplied to a biosensor chip and a measuring device therefor.

  Conventionally, research on bioelectronics in which biological functions are applied to the electronics field has been progressing. The biosensor chip in the bioelectronics field is a device that uses an excellent molecular identification function of a living body, and is promising in the future as being capable of measuring chemical substances quickly and easily. Such a biosensor chip is applied as a sensor for measuring a small amount of sample. For example, the biosensor chip is used for a home health check (self-care) for self-management and prevention of diabetes by measuring a blood glucose level and a urine sugar level, or industrially. Is widely used in applications such as sampling quality inspection of products on the production line.

  As a specific example of measurement, a sample containing a measurement target substance is collected and dropped into a reaction part, and for example, a reduction product generated by an enzyme reaction is oxidized to detect and detect an element current value due to the oxidation. A measured value equivalent to the element current value is obtained by referring to a data table, and is output and displayed (see Patent Document 1).

Incidentally, a basic circuit of a biosensor system for measuring biological information based on a biological substance using a biosensor chip is shown in FIG. This biosensor system includes a biosensor chip 1 and a measuring instrument 2 that measures biological information of a biological substance supplied to the biochip sensor 1. Among these, the biosensor chip 1 includes a reaction unit 4 that is provided so as to be connected to the plurality of sensor electrodes 3a and 3b and to which a biological substance is supplied (dropped).

For example, the reaction unit 4 is configured for blood glucose level reaction, and is formed of a mixture of an oxidoreductase and an electron conductor (mediator), for example, a mixture of glucose oxidase and ferricyanide.
The measuring instrument 2 includes an insertion unit 5, connector electrodes 6 a and 6 b, a voltage switch 7, an amplifier circuit 8, a control unit 10 including a biological information measurement unit 9 and a memory 15.

  Among these, the insertion part 5 makes the form in which the front-end | tip part of the biosensor chip 1 can be inserted. The connector electrodes 6a and 6b are provided so as to come into contact with the sensor electrodes 3a and 3b when the biosensor chip 1 is inserted into the insertion portion 5. The connector electrode 6b is grounded. The voltage switch 7 functions to switch and input either the reference voltage (Vref) or the ground potential set on the control unit 10 side to the reaction unit 4 at a predetermined timing.

Further, when the reference voltage (Vref) is applied to the non-inverting input terminal (+) of the amplifier circuit 8 and the current from the reaction unit 4 is input to the inverting input terminal (−), the output value converted into the voltage. Is output to the control unit 10.
The biological information measuring unit 9 is connected so that the output value of the amplifier circuit 8 is input, and functions to obtain biological information based on the output value of the amplifier circuit 8. Specifically, the biological information measuring unit 9 functions to convert the current value from the reaction unit 4 into a blood glucose level (biological information) with reference to a data table stored in the memory 15 and display the blood glucose level on the display unit 25. To do.
The amplifier circuit 8 includes an operational amplifier (operational amplifier) 11 and a feedback resistor (for setting amplification factor) 12 that connects the inverting input terminal (−) and the output terminal of the operational amplifier 11. The inverting input terminal (−) of the operational amplifier 11 is connected to the connector electrode 6 a, and the non-inverting input terminal (+) can be selectively connected to the reference voltage (Vref) or the ground potential via the voltage changeover switch 7. .

  When the voltage switch 7 is connected to the ground potential side, the potential applied to the reaction unit 4 via the operational amplifier 11, the sensor electrodes 3a and 3b, and the connector electrodes 6a and 6b is 0 [V] potential. is there.

  On the other hand, when the voltage changeover switch 7 is connected to the reference voltage (Vref) side, the reference voltage is applied to the reaction unit 4 via the operational amplifier 11, the sensor electrodes 3a and 3b, and the connector electrodes 6a and 6b. By applying this reference voltage, a current value that flows due to a potential difference between both ends of the reaction unit 4 is converted into an output value of a voltage by the amplifier circuit 8 and input to the control unit 10.

  FIG. 6 is a perspective view showing an outline of the entire biosensor system including the biosensor chip 1 and the measuring device 2. In FIG. 6, the measuring instrument 2 forms a casing 23 composed of a lower case 21 and an upper case 22. The insertion portion 5 into which the biosensor chip 1 is inserted is provided at the front center portion of the housing 23 so as to open. Circular operation buttons 24 are provided on the left and right rear with the insertion portion 5 as the center. Further behind these operation buttons 24, a rectangular display unit 25 for displaying measurement values and the like is provided.

  The insertion portion 5 is provided with connector electrodes 6a and 6b that can be electrically contacted with the sensor electrodes 3a and 3b of the biosensor chip 1. These electrodes 3a, 3b, 6a and 6b are made of conductive metals such as gold, silver, platinum, palladium, nickel, copper and iridium, as well as non-metallic materials such as carbon and conductive plastics.

  On the other hand, the biosensor chip 1 includes a stick-like insulating substrate 26 that can be inserted into the insertion portion 5 of the measuring instrument 2 and two sensor electrodes 3 a and 3 b provided on the insulating substrate 26. A reaction part 4 for supplying biological material (dropping) is provided at the end opposite to the side inserted into the insertion part 5 so as to be electrically connectable to the sensor electrodes 3a and 3b.

Next, the operation of this biochip system will be described with reference to the timing chart of FIG.
First, the voltage changeover switch 7 is switched to the reference voltage side by a switch control signal output from the control unit 10, and the biosensor chip 1 is inserted into the insertion unit 5 of the measuring instrument 2 in this state.
At this time, the reference voltage is applied to the reaction unit 4 via the operational amplifier 11 (non-inverting input terminal (+) and inverting input terminal (−)), the sensor electrodes 3a and 3b, and the connector electrodes 6a and 6b.

  After inserting the biosensor chip 1 into the insertion part 5 in this way, a biological substance, here blood, is supplied (dropped) onto the reaction part 4 at t2 when a predetermined time has elapsed. As shown in FIG. 7B, the reaction current flowing through the reaction unit 4 due to the dripping of blood rises instantaneously. The controller 10 recognizes this drop of blood based on a pulsed current that rises instantaneously.

Subsequently, the control unit 10 switches the voltage changeover switch 7 from the reference voltage to the ground potential for a predetermined time from the time when the pulsed current at the time of recognition of the dropping is settled. Thereby, the voltage applied to the reaction part 4 via the operational amplifier 11, the sensor electrodes 3a and 3b, and the connector electrodes 6a and 6b is instantaneously reduced to 0 [V].
The control unit 10 maintains the voltage 0 [V] applied to the reaction unit 4 for a preset time, and accumulates charges generated by the blood chemistry (enzyme) reaction in the reaction unit 4 during this time.

  Next, the control unit 10 switches the voltage changeover switch 7 to the reference voltage side again at time t3 when a predetermined time has elapsed from time t2. As a result, a constant reference voltage (Vref) is applied to both ends of the reaction unit 4 as shown in FIG. As a result, a reaction current corresponding to a change in resistance value based on the enzyme reaction flows through the reaction unit 4.

The reaction current has a tendency to gradually decrease according to the discharge time constant of the charge after sharply rising to a predetermined level when a reference voltage is applied. The reaction current value at a predetermined timing t4 near the end of the gradual decrease of the reaction current is sampled and converted into an equivalent biological information value (blood glucose level, etc.) with reference to a data table stored in the memory 15, Displayed on the display unit 25.
JP-A-11-108879

  However, in the method for measuring biological information by the conventional biosensor system, for example, the measurement of the blood glucose level takes a long time of several tens of seconds. Therefore, by applying some stress to the biosensor chip 1 during that time, the sensor electrode The connection between 3a and 3b and the connector electrodes 6a and 6b may be instantaneously disconnected. When the applied voltage to the reaction unit 4 is 0 [V], there is no problem, but as shown in FIG. 7C, the sensor electrodes 3a, 3b are applied during the application of the applied voltage after t3, that is, during the measurement of the reaction current. And the connector electrodes 6a and 6b are instantaneously disconnected, the reaction current value flowing through the reaction unit 4 falls for a moment and then is connected again to rise.

Accordingly, during the period from the falling to the rising, the charge accumulation by the enzyme reaction is resumed in the same manner as that performed during the standing time. For this reason, when the sensor electrodes 3a, 3b and the connector electrodes 6a, 6b are connected again, the rising level of the reaction current detected by the control unit 10 is higher than the level of the reaction current at the deviated timing. Become. As a result, the measurement result k2 of the normal reaction current at the measurement time t4 becomes abnormally high as shown in FIG. 7C compared to the value k1 in the case shown in FIG. That is, there is a problem that incorrect biological information is obtained due to the sensor electrode being detached, and correct health management cannot be realized.

  In addition, various methods for providing a dedicated terminal for chip removal have been proposed for detecting a biosensor chip disconnection. However, the chip size of the biosensor chip is basically increased and an increase in cost is unavoidable. There was an inconvenience.

Therefore, the object of the present invention is to sample the reaction current during the application time of the applied voltage and compare the reaction current values before and after sampling without providing a dedicated terminal for detection of chip detachment. Accordingly, it is an object of the present invention to provide a biosensor system and a measuring instrument that can quickly and surely detect a sensor electrode disconnection of a biosensor chip used for biological information measurement.

To achieve the above object, a biosensor system according to the present invention is a biosensor system comprising a biosensor chip and a measuring instrument that measures biological information of a biological material supplied to the biosensor chip. ,
The biosensor chip is provided so as to be electrically connected to a plurality of sensor electrodes, and has a reaction part to which the biological material is supplied,
The measuring instrument is
An insertion part capable of inserting the biosensor chip;
A connector electrode provided in contact with the sensor electrode by inserting the biosensor chip into the insertion portion;
A biological information measuring unit that obtains biological information by measuring a reaction current from the reaction unit;
The reaction current is sampled a plurality of times at predetermined time intervals, and when the sampled current value exceeds the previously sampled current value, it is detected that the sensor electrode is instantaneously disconnected from the connector electrode and reconnected. A sensor electrode disconnection detector;
It is characterized by having.

The measuring device according to the present invention is
An insertion part of a biosensor chip provided to be electrically connected to a plurality of sensor electrodes and having a reaction part to which a biological material is supplied;
A connector electrode provided in contact with the sensor electrode by inserting the biosensor chip into the insertion portion;
A biological information measuring unit that obtains biological information by measuring a reaction current from the reaction unit;
The reaction current is sampled a plurality of times at predetermined time intervals, and when the sampled current value exceeds the previously sampled current value, it is detected that the sensor electrode is instantaneously disconnected from the connector electrode and reconnected. A sensor electrode disconnection detector;
It is characterized by providing.

  According to the present invention, during application of a voltage to the reaction part, the reaction current shows a gradual decrease tendency due to the discharge of the charge accumulated in the reaction part. By comparing the reaction current levels before and after, it is possible to quickly and accurately determine that the sensor electrode of the biosensor chip has instantaneously disconnected from the connector electrode on the measuring instrument side. Among them, it is possible to adopt only accurate measurement values and display them on the display unit so that the measurement subject or the like can widely recognize them.

  Hereinafter, a biosensor system according to an embodiment of the present invention will be described in detail with reference to the drawings. In the present embodiment, an example of a biosensor system in which blood is raised as an example of a biological material supplied to a biosensor chip and the measuring device measures a blood glucose level in the blood will be described.

  FIG. 1 is a block diagram showing a biosensor system according to the present embodiment, FIG. 2 is a timing chart of current and voltage in each part of the biosensor system according to the present embodiment, and FIG. 3 is a biological material in the biosensor system according to the present embodiment. FIG. 4 is a waveform diagram showing the reaction current in FIG. 2 in detail.

In FIG. 1, the biosensor system includes a biosensor chip 1 and a measurement unit 2 </ b> A that measures biological information of blood (biological material) supplied to the biosensor chip 1. Among these, the biosensor chip 1 has sensor electrodes 3a and 3b and a reaction part 4, and has the same connection form as that shown in FIG.
The measuring instrument 2A includes an amplifier circuit 8 including a connector electrode 6a, 6b, an operational amplifier (operational amplifier) 11 and a feedback resistor 12, and a voltage changeover switch 7, and has the same connection configuration as that shown in FIG. .

  The measuring instrument 2 </ b> A includes a sensor electrode detachment detection unit, a counter 14, and a memory 15 in addition to the biological information measurement unit 9. Among these, the biological information measuring unit 9 raises the applied voltage to the reaction unit 4 to a predetermined level by inserting the biosensor chip 1 into the insertion unit 5 when the reference voltage is input, as described above, and the reaction unit 4 After the blood is supplied, the applied voltage to the reaction unit 4 is left at a predetermined time of 0 [V] to promote the generation of charges by the enzymatic reaction of the blood, and the applied voltage at the predetermined level is again set within the set time. After starting up again, the reaction current value due to the charge release of the reaction section 4 within a predetermined time is measured.

  Further, the counter 14 outputs a sampling signal having a set period, and the reaction current value gradually decreased by the sensor electrode detachment detection unit 13 can be sampled according to the sampling signal. The memory 15 stores a data table having blood glucose level information corresponding to the measured value of the reaction current as described above, and functions to temporarily store each sampled current value. As a result, the sensor electrode detachment detection unit 13 can compare each sampled current value with each previous sampled current value.

Next, the operation of the biosensor system of this embodiment will be described with reference to the timing chart of FIG. 2 and the flowchart of FIG.
First, at t1, the voltage changeover switch 7 is switched to the reference voltage side by a switch control signal output from the control unit 10, and the biosensor chip 1 is inserted into the insertion unit 5 of the measuring instrument 2 in this state.
At this time, the reference voltage is applied to the reaction unit 4 via the operational amplifier 11 (non-inverting input terminal (+) and inverting input terminal (−)), the sensor electrodes 3a and 3b, and the connector electrodes 6a and 6b.

  After inserting the biosensor chip 1 into the insertion portion 5 in this way, at time t2 when a predetermined time has elapsed, a biological material, here blood, is supplied (dropped) onto the reaction portion 4. The reaction current flowing through the reaction part 4 due to the dripping of blood rises instantaneously as shown in FIGS. 2 (b) and 2 (c). The controller 10 recognizes this drop of blood based on a pulsed current that rises instantaneously.

Subsequently, the control unit 10 switches the voltage changeover switch 7 from the reference voltage to the ground potential for a predetermined time from the time when the pulsed current at the time of recognition of the dropping is settled. Thereby, the voltage applied to the reaction part 4 via the operational amplifier 11, the sensor electrodes 3a and 3b, and the connector electrodes 6a and 6b is instantaneously reduced to 0 [V].
The control unit 10 maintains the voltage 0 [V] applied to the reaction unit 4 for a preset time, and accumulates charges generated by the blood chemistry (enzyme) reaction in the reaction unit 4 during this time.

  Next, the control unit 10 switches the voltage changeover switch 7 to the reference voltage (Vref) side again at time t3 when a predetermined time has elapsed from time t2. As a result, a constant reference voltage (Vref) is applied to both ends of the reaction unit 4 as shown in FIG. As a result, a reaction current corresponding to a change based on the enzyme reaction flows through the reaction unit 4.

  Thereafter, as shown in the flowchart of FIG. 3, the control unit 10 starts the counter 14 together with the start of application of the reference voltage (t3) (step S1). During the reference voltage application period, the sensor electrode detachment detector 13 samples the reaction current according to the count timing of the counter 14. That is, after the rise of the applied voltage, the current value A (n) is measured and sampled for each of s1, s2,... Sn at a constant period (for example, several 100 msec) (step S2).

  In addition, the sensor electrode detachment detection unit 13 temporarily stores the sampled current values A (n) in the memory 15 one after another, and compares the current values A (n−1) sampled with each time. Such current value collection, storage in the memory 15, and comparison with the current value sampled last time are performed for each time of s1 to sn (step S3).

  When the sensor electrodes 3a and 3b and the connector electrodes 6a and 6b are securely connected without being disconnected (in the case of a normal reaction current in FIG. 2B), during the application of the reference voltage, The reaction current that flows into the biological information measurement unit 9 due to the accumulated charge has a characteristic of drawing a gradual decrease curve similar to the conventional one.

However, the sensor electrode out of the biosensor chip 1, the sensor electrodes 3a, 3b is connector electrodes 6a, when the momentary contact failure or non-contact state from 6b, the accumulation of charge to the active portion 4 therebetween is resumed. For this reason, even if the sensor electrode disconnection is subsequently eliminated and a normal applied voltage is applied to the control unit 10, the reaction current becomes higher than the value at the time of sensor electrode disconnection occurrence (FIG. 2 (c)) For reaction current).

Therefore, when the reaction current is equal to or greater than the value at the time of occurrence of sensor electrode disconnection by the comparison of the reaction current value by the sensor electrode disconnection detection unit 13, the reaction current is measured. It is detected that the result is abnormal (step S4). Thereby, it can be determined that the sensor electrode has been detached.

On the other hand, when the comparison result of the measured values at s1 to sn is normal, that is, when A (n) <A (n-1), the reaction current tends to gradually decrease as described above. Therefore, reaction current is always lower than the value of the time of occurrence off sensor electrodes, it can be determined that the sensor electrode out has not occurred.

  Next, it is determined whether or not the count value n of the reaction current has reached the application time s of the applied voltage (step S5). If the application time s has been reached, the measurement result is displayed on the display unit 25 shown in FIG. Displayed above (step S6). On the other hand, when the count value n exceeds the application time of the applied voltage, 1 is added to the count value n (step S7), and the next measurement value sampling (step S2) and the processing after this sampling are performed. Transition.

  FIG. 4 is a waveform diagram showing a measured value waveform of a reaction current in the gradual decrease process. According to this, the reaction current rises at the timing t3 when the applied voltage is applied following the predetermined standing time, and gradually decreases to t4. The reaction current value at t4 becomes the measurement current value.

  As described above, in the present embodiment, the biological information measurement unit 9 raises the voltage applied to the reaction unit 4 to a predetermined level by inserting the biosensor chip 1 into the insertion unit 5 when the reference voltage is input. After supplying the biological material, the applied voltage to the reaction unit 4 is left at a potential of 0 [V] for a predetermined time to promote the generation of charges by the enzymatic reaction of the biological material, and the applied voltage at the predetermined level is again set within the set time. Then, the reaction current value generated from the reaction unit 4 at a predetermined timing after being started up again is used as a measurement result, and the sensor electrode detachment detection unit 13 samples the reaction current a plurality of times at predetermined time intervals, and the sampled current value is It is configured to detect that the sensor electrodes 3a and 3b are disconnected from the connector electrodes 6a and 6b when the current value sampled previously is exceeded. .

Therefore, without providing a dedicated terminal for detecting the chip-off of the biosensor chip 1, and sampling the reaction current during the application time of the applied voltage, and comparing the reaction current values before and after sampling, the biological information It is possible to quickly and reliably detect the sensor electrode detachment of the biosensor chip 1 used for measurement.

It is a block diagram which shows the biosensor system which concerns on this embodiment. It is a timing chart of the electric current in each part of the biosensor system concerning this embodiment, and voltage. It is a flowchart which shows the measurement procedure of the biometric information in the biosensor system which concerns on this embodiment. It is a wave form diagram which shows the reaction current in FIG. 2 in detail. It is a block diagram which shows a general biosensor system. It is a perspective view which shows the external appearance of a biosensor system. It is a timing chart of the voltage in each part of the biosensor system shown in Drawing 5, and current.

DESCRIPTION OF SYMBOLS 1 Sensor chip 2 Measuring device 3a, 3b Sensor electrode 4 Reaction part 5 Insertion part 6a, 6b Connector electrode 7 Voltage changeover switch 8 Amplifying circuit 9 Biometric information measurement part 10 Control part 11 Operational amplifier 12 Resistance 13 Sensor electrode removal detection part 14 Counter 15 memory

Claims (2)

A biosensor system comprising: a biosensor chip; and a measuring instrument that measures biological information of a biological material supplied to the biosensor chip,
The biosensor chip is provided so as to be electrically connected to a plurality of sensor electrodes, and has a reaction part to which the biological material is supplied,
The measuring instrument is
An insertion part capable of inserting the biosensor chip;
A connector electrode provided in contact with the sensor electrode by inserting the biosensor chip into the insertion portion;
A biological information measuring unit that obtains biological information by measuring a reaction current from the reaction unit;
The reaction current is sampled a plurality of times at predetermined time intervals, and when the sampled current value exceeds the previously sampled current value, it is detected that the sensor electrode is instantaneously disconnected from the connector electrode and reconnected. A sensor electrode disconnection detector;
A biosensor system comprising: An insertion part of a biosensor chip provided to be electrically connected to a plurality of sensor electrodes and having a reaction part to which a biological material is supplied;
A connector electrode provided in contact with the sensor electrode by inserting the biosensor chip into the insertion portion;
A biological information measuring unit that obtains biological information by measuring a reaction current from the reaction unit;
The reaction current is sampled a plurality of times at predetermined time intervals, and when the sampled current value exceeds the previously sampled current value, it is detected that the sensor electrode is instantaneously disconnected from the connector electrode and reconnected. A sensor electrode disconnection detector;
A measuring instrument comprising:

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