JP4441019B2 - Sensor cleaning method, sensor cleaning device, measuring method and measuring device - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a sensor cleaning technique for performing measurement with high accuracy and preventing deterioration of a sensor in a measuring apparatus that uses a sensor to determine a characteristic value of a measurement target.
[0002]
[Prior art]
Among various measuring devices, a sensor that uses a sensor to determine a characteristic value of a measurement object changes the characteristics of the sensor depending on the substance attached to the sensor.
[0003]
For example, in a measuring apparatus for analyzing a component of a substance contained in a liquid, a molecular film made of an amphiphilic substance or a bitter substance is used as a sensor.
[0004]
This molecular film sensor utilizes the action of changing the membrane potential according to the components in the liquid when immersed in the liquid. When actually measuring a sample liquid using this sensor, Based on the potential of the membrane when the molecular membrane sensor is immersed in the reference solution, the amount of change in the potential of the membrane when immersed in the sample solution or the potential of the membrane when immersed in the reference solution again after being immersed in the sample solution The amount of change is obtained as a characteristic value of the sample, and the components in the sample liquid are analyzed based on the characteristic value.
[0005]
When such a measurement is continuously performed for a plurality of samples with the same molecular film sensor, if the substance contained in the sample measured before is adsorbed to the molecular film sensor, the response characteristic of the molecular film sensor Changes to affect the next measurement.
[0006]
For this reason, conventionally, after each measurement of a sample, the molecular film sensor is washed, and then the next measurement is performed.
[0007]
This cleaning is performed, for example, by vibrating the molecular film sensor in the cleaning liquid for a certain period of time. The components and cleaning time of the cleaning liquid depend on the types of molecular film sensors and the components expected from the sample collection source. It was decided.
[0008]
[Problems to be solved by the invention]
However, when measuring a sample whose component is completely unknown or a sample in which the component or concentration of the contained substance changes, as described above, in the conventional method in which the sensor is simply washed for a certain period of time, the response of the sensor due to insufficient washing. There has been a problem that the characteristics are greatly changed, the reproducibility and accuracy of the measurement are lowered, or the sensor is deteriorated due to excessive washing.
[0009]
An object of the present invention is to provide a sensor cleaning method, a cleaning apparatus, a measuring method, and a measuring apparatus that solve this problem and perform measurement with high reproducibility and accuracy and do not deteriorate the sensor.
[0010]
[Means for Solving the Problems]
In order to achieve the above object, a sensor cleaning method according to claim 1 of the present invention comprises:
A cleaning stage for cleaning the sensor for a predetermined time;
A measurement stage for measuring a reference measurement object by a sensor washed for a predetermined time;
A determination step of determining whether or not the measurement value for the reference measurement object is within a preset allowable range,
The cleaning step to the determination step are repeated until the measurement value for the reference measurement object falls within the allowable range.
[0011]
The sensor cleaning device according to claim 2 of the present invention is
Cleaning means for cleaning the sensor;
Measuring means for measuring a measurement object serving as a reference by the sensor;
Determination means for determining whether or not the measurement value obtained by the measurement means is within a preset allowable range;
Control means for alternately repeating the cleaning by the cleaning means and the measurement by the measuring means until the determination means determines that the measured value is within a preset allowable range.
[0012]
Moreover, the measuring method of claim 3 of the present invention comprises:
In a measurement method that performs measurement using a sensor that outputs a signal in response to the measurement target,
A cleaning step of cleaning the sensor for a predetermined time;
A first measurement step of measuring a first measurement object serving as a reference by the sensor washed for a predetermined time;
A determination step of determining whether or not a measurement value for the first measurement object is within a preset allowable range;
Repeating the cleaning step to the determination step until the measurement value for the first measurement object falls within the allowable range;
A second measurement stage in which a second measurement object is measured by a sensor whose measurement value for the first measurement object is within the allowable range;
Obtaining a difference between a final measurement value obtained by measurement for the first measurement object and a measurement value obtained by measurement for the second measurement object as a characteristic value of the second measurement object. It is characterized by that.
[0013]
Moreover, the measuring device of claim 4 of the present invention comprises:
A sensor that outputs a signal in response to the measurement object;
Cleaning means for cleaning the sensor;
First measurement means for measuring a first measurement object serving as a reference by the sensor;
Determination means for determining whether or not the measurement value obtained by the first measurement means is within a preset allowable range;
A cleaning control unit that alternately repeats the cleaning by the cleaning unit and the measurement by the first measuring unit until the determination unit determines that the measured value is within a preset allowable range;
Reference value storage means for storing, as a reference value, a measurement value when it is determined by the determination means that the measurement value is within a preset allowable range;
Second measurement means for measuring a second measurement object by the sensor from which the measurement value within the allowable range is obtained for the first measurement object;
Characteristic value calculation means for calculating a difference between the measurement value obtained by the second measurement means and the reference value stored in the reference value storage means as the characteristic value of the second measurement object. .
[0014]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 shows a configuration of a measuring apparatus 20 for analyzing a component of a substance contained in a liquid using a molecular film sensor.
[0015]
The measuring apparatus 20 is provided with a plurality of containers 21, of which the container 21 (1) stores the cleaning liquid Lc, the container 21 (2) stores the reference liquid Lr, and the other containers 21 ( 3), 21 (4),... Contains the sample liquid Lx.
[0016]
Here, the reference solution Lr and the cleaning solution Lc are the same, and an aqueous solution of potassium chloride (30 mM) and tartaric acid (0.3 mM) is used. As described above, the components of the cleaning liquid need to be determined according to the type of molecular film of the molecular film sensor and the components included in or expected to be included in the sample liquid, and therefore, the reference liquid Lr and the cleaning liquid Lc. May not be the same.
[0017]
The container 21 (1) in which the cleaning liquid Lc is stored is provided with a vibration device 22 that constitutes a cleaning unit of the measuring device 20 together with the cleaning liquid Lc and a control device 40 described later. This vibration device 22 generates ultrasonic waves, vibrates the cleaning liquid Lc in the container 21 (1), and cleans what is in the cleaning liquid Lc.
[0018]
The probe 25 is immersed in the liquid stored in these containers 21. The probe 25 includes a reference electrode 26 and a molecular film sensor 30.
[0019]
The reference electrode 26 determines a reference potential, and the surface thereof is covered with a buffer layer 27 obtained by solidifying 100 mM potassium chloride with agar, and a lead wire 25a is connected thereto.
[0020]
In the molecular film sensor 30, a molecular film 32 is fixed on the surface of a base material 31 such as acrylic, and the opposite surface of the molecular film 32 is interposed through a buffer layer 33 that is the same as the buffer layer 27 of the reference electrode 26. An electrode 34 is provided, and a lead wire 25 b is connected to the electrode 34.
[0021]
This molecular film 32 is formed by mixing an amphipathic substance or a bitter substance such as lipid, a plasticizer, and a polymer material. Here, as the molecular film having a positive polarity, 50 mg of TDA (tetradodecyl ammonium bromide) having a carbon chain length of 12 (R = 12) in the lipid of the quaternary ammonium salt, 1 ml of DOPP (dioctyl phenyl phosphonate) as a plasticizer, and a polymer material A mixture of 800 mg of PVC (polyvinyl chloride) is dissolved in 10 ml of THF (tetrahydrofuran), and this is heated in a flat bottom container (for example, a 85 mmφ petri dish) at about 30 ° C. for 2 hours to volatilize THF. The thing of thickness 200micrometer obtained by this is used.
[0022]
Here, the molecular film sensor 30 having one molecular film 32 having a positive polarity that strongly adsorbs a negatively charged substance such as tannin will be described. However, the molecular film sensor 30 has a plurality of molecules having different characteristics. A structure having a film and selecting a plurality of molecular films may be used.
[0023]
The probe 25 is supported by the moving device 35. The moving device 35 moves the reference electrode 26 of the probe 25 and the molecular film sensor 30 so as to be immersed in the liquid stored in each container 21 described above. Although the probe 25 is moved here, the probe 25 may be immersed in the liquid in the container 21 by moving the container 21 side by the moving device 35.
[0024]
Lead wires 25 a and 25 b of the probe 25 are connected to the voltage detector 36. The voltage detector 36 detects the voltage of the molecular film sensor 30 based on the potential of the reference electrode 26 and outputs it to the A / D converter 37.
[0025]
The A / D converter 37 converts the output of the voltage detector 20 into a digital value and outputs it to the arithmetic unit 38.
[0026]
The arithmetic device 38 performs storage processing and arithmetic processing on the output of the A / D converter 21 in accordance with instructions from the control device 40 described later, and outputs the result to the output device 39.
[0027]
The output device 39 includes a display device, a printer, and the like, and displays and outputs the processing result of the arithmetic device 38.
[0028]
The vibration device 22, the moving device 35 and the arithmetic device 38 are controlled by the control device 40. Note that the arithmetic device 38 and the control device 40 are constituted by, for example, a microcomputer.
[0029]
2 and 3 are flowcharts showing the processing procedure of the arithmetic device 38 and the control device 40. FIG. Hereinafter, the operation of the measuring apparatus 20 will be described based on these flowcharts.
[0030]
The process of FIG. 2 is a relative value measurement process for a plurality of N sample liquids Lx (1) to Lx (N). First, the number i designating the sample liquid is initialized to 1, and the probe 25 is set to the reference liquid. The film surface is stabilized with respect to the molecular film sensor 30 by being immersed in Lr, the reference liquid Lr is measured, and the voltage obtained by the measurement is stored as the initial value Vr of the reference voltage Vrr (S1 to S3). .
[0031]
This film surface stabilization treatment is for activating and stabilizing the film surface of the molecular film 32 of the probe 25 that has not been used for a long time. (It may be times) The operation of obtaining the voltage when a certain time (for example, 30 seconds) has passed since the vertical movement is repeated, and the difference between the voltage obtained last time and the voltage obtained this time is within a predetermined value (for example, 0.5 mV) Is determined to be stable.
[0032]
Next, the probe 25 is immersed in the sample liquid Lx (i), and the voltage V at that time is obtained (second measuring means). The difference between the voltage V and the reference voltage Vrr (initial value is equal to Vr) The voltage V (i) = V−Vrr is obtained as a characteristic value (referred to as a relative value) of the sample liquid Lx (i) (characteristic value calculating means) (S4 to S6).
[0033]
Then, after immersing the probe 25 in the cleaning liquid Lc and applying ultrasonic vibration from the vibration device 22 for a predetermined time (for example, several tens of seconds to several minutes) to clean the probe 25 (cleaning means), the probe 25 is used as the reference liquid Lr. Immerse and determine the voltage Vc at that time (first measuring means) (S7 to S10).
[0034]
As described above, in the case of this embodiment, since the components of the cleaning liquid Lc and the reference liquid Lr are the same, the cleaning liquid Lc is used as the reference liquid, and as shown by the broken line in FIG. After applying the sonic vibration for a predetermined time, the voltage Vc may be obtained as it is without moving the probe 25 to the reference liquid Lr.
[0035]
Next, it is determined whether or not the obtained voltage Vc is within a predetermined allowable range set for the initial value Vr of the reference voltage (determination means) (S11).
[0036]
Here, as shown in FIG. 4, the allowable range is set to a range of (Vr−α) to (Vr + α) centering on the initial value Vr of the reference voltage.
[0037]
The value α that determines the width of the allowable range is set to, for example, a value βVr obtained by multiplying the voltage Vr by a predetermined allowable ratio β (for example, 0.02), a fixed value that does not depend on the voltage Vr (for example, 0.3 mV), or the like. .
[0038]
If the voltage Vc is not within the allowable range, the processes S7 to S11 are repeated until the voltage Vc falls within the allowable range (cleaning control unit). As described above, when the cleaning liquid Lc is used as the reference liquid, the processes S8 to S11 are repeated with the process 9 omitted as indicated by the broken line.
[0039]
By repeating this process, the substance adsorbed on the film surface of the molecular film sensor 30 is removed, and the voltage Vc gradually approaches Vc1, Vc2,... Each time cleaning is performed as shown in FIG. For example, the voltage Vc4 after the fourth cleaning is within the allowable range.
[0040]
In this way, when it is determined that the voltage Vc is within the allowable range, it is assumed that the cleaning is completed, the reference voltage Vrr is updated with the voltage Vc at this time (reference value storage means), and the next sample liquid is added. After the designation, the process returns to the process S4 (S12 to S14).
[0041]
Thereafter, the processes S4 to S14 are repeated to obtain characteristic values (relative values) V (1) to V (N) for the plurality of sample liquids Lx (1) to Lx (N). Thus, the components of the sample liquid can be analyzed.
[0042]
3 is a CPA measurement process for a plurality of N sample liquids Lx (1) to Lx (N), and the processes S21 to S24 are the same as the processes S1 to S4 in FIG. The probe 25 immersed in Lx (i) is returned to the reference liquid Lr to obtain the voltage V ′ at that time (second measuring means), and the voltage of the difference between this voltage V ′ and the reference voltage Vrr (initial value Vr) V (i) = V′−Vrr is obtained as a characteristic value (referred to as CPA value) of the sample liquid Lx (i) (characteristic value calculation means) (S21 to S27).
[0043]
In CPA measurement, before returning the probe 25 soaked in the sample liquid Lx (i) to the reference liquid Lr, lightly removes components with low adsorptivity from the components of the sample liquid on the surface of the molecular film 32. May be washed.
[0044]
Further, the cleaning process portion (S28 to S35) in the process of FIG. 3 is the same as the processes S7 to S14 of FIG.
[0045]
That is, the probe 25 is immersed in the cleaning liquid Lc, ultrasonic vibration is applied by the vibration device 22 for a predetermined time to clean the probe 25 (cleaning means), and then the probe 25 is immersed in the reference liquid Lr to obtain the voltage Vc at that time. (First measuring means) (S28 to S31).
[0046]
Also in this case, since the components of the cleaning liquid Lc and the reference liquid Lr are the same, the cleaning liquid Lc is used as the reference liquid, and after applying ultrasonic vibration by the vibration device 22 for a predetermined time, as shown by the broken line in FIG. The voltage Vc may be obtained as it is without moving the probe 25 to the reference liquid Lr.
[0047]
Next, it is determined whether or not the voltage Vc is within an allowable range set for the voltage Vr (determination means) (S32).
[0048]
If the voltage Vc is not within the allowable range, the processes S28 to S32 are repeated until the voltage Vc falls within the allowable range (cleaning control means). As described above, when the cleaning liquid Lc is used as the reference liquid, the processes S29 to S32 are repeated with the process 30 omitted as indicated by the broken line.
[0049]
Then, it is assumed that the cleaning is completed when the voltage Vc falls within the allowable range, the reference voltage Vrr is updated with the voltage Vc at this time (reference value storage means), the next sample liquid is designated, and the process proceeds to step S24. Return (S33 to S35).
[0050]
Thereafter, the processes S24 to S35 are repeated to obtain characteristic values (CPA values) V (1) to V (N) for the plurality of sample liquids Lx (1) to Lx (N). The component analysis of the sample liquid can be performed from the value.
[0051]
As described above, in this measuring apparatus 20, the molecular film sensor 30 is washed for a predetermined time (S8, S28), and the reference liquid Lr is measured by the molecular film sensor 30 washed for a predetermined time (S9, S10, S30, S31). The process of determining whether or not the measurement value Vc for the reference liquid Lr is within a preset allowable range (S11, S32) is repeated until the measurement value Vc for the reference liquid Lr falls within the allowable range.
[0052]
For this reason, the necessary minimum cleaning is always performed on the substance adsorbed on the molecular film sensor 30, and even when the components of the sample liquid are unknown, the cleaning is insufficient and the response characteristics of the molecular film sensor greatly change. Or over-cleaning prevents the sensor from deteriorating.
[0053]
Further, in this measuring device 20, after the voltage Vc when the cleaning is completed as described above is stored as a reference value, the next sample solution is measured, and the difference between the measured value and the reference value is calculated. It is calculated as a characteristic value.
[0054]
For this reason, measurement of a new sample liquid can be started from a state in which the film surface of the molecular film sensor 30 is always substantially the same, measurement with high reproducibility and accuracy can be performed, and component analysis in the liquid is high. Can be done with precision.
[0055]
In the above-described embodiment, the molecular film sensor 30 is cleaned by applying ultrasonic vibration to the cleaning liquid having the same component as the reference liquid. However, in the cleaning liquid containing an organic solvent such as ethanol different from the reference liquid, Cleaning can also be performed by vibrating the membrane sensor 30 or by allowing the cleaning liquid to flow through the molecular membrane sensor 30 in a shower.
[0056]
Moreover, although the said description demonstrated the measuring apparatus 20 using the molecular film sensor 30, this invention also relates to the sensor which a response characteristic may change by adsorption | suction of a measuring object, and a measuring apparatus using the sensor. Applicable.
[0057]
The cleaning according to the present invention is not limited to liquid cleaning, but may be any method for removing substances that change the characteristics of the sensor. It is also possible to perform cleaning (cleaning) with a brush or cleaning (cleaning) with air.
[0058]
【The invention's effect】
As described above, the sensor cleaning method and the sensor cleaning apparatus according to the present invention clean the sensor for a predetermined time, measure the reference measurement object by the sensor cleaned for the predetermined time, and the measured value is within a preset allowable range. The process of determining whether or not the measured value is within the allowable range is repeated.
[0059]
For this reason, the necessary minimum cleaning is always performed on the substance adsorbed on the sensor. Even when the adsorptivity of the object to be measured is unknown, the response characteristics of the sensor may change greatly due to insufficient cleaning. The sensor does not deteriorate due to excessive.
[0060]
Further, in the measurement method and the measurement apparatus of the present invention, the difference between the measurement value obtained by performing the measurement on the second measurement object and the reference value, using the measurement value when the cleaning is completed as described above as the reference value. Is obtained as the characteristic value of the second measurement object.
For this reason, measurement can always be started from a constant state of the sensor, and measurement with high reproducibility and accuracy can be performed.
[Brief description of the drawings]
FIG. 1 is a diagram showing a configuration of an embodiment of the present invention. FIG. 2 is a flowchart showing a processing procedure of a main part of the embodiment. FIG. 3 is a flowchart showing a processing procedure of a main part of the embodiment. To explain the operation of the [Description of symbols]
20 Measuring Device 21 Container 22 Vibrating Device 25 Probe 26 Reference Electrode 30 Molecular Film Sensor 35 Moving Device 36 Voltage Detector 37 A / D Converter 38 Arithmetic Device 39 Output Device 40 Controller Lr Reference Solution Lc Cleaning Solution Lx Sample Solution

Claims (4)

A cleaning stage for cleaning the sensor for a predetermined time;
A measurement stage for measuring a reference measurement object by a sensor washed for a predetermined time;
Determining whether the measurement value for the reference measurement object is within a preset allowable range,
A sensor cleaning method, wherein the cleaning step to the determination step are repeated until a measurement value for the reference measurement object falls within the allowable range. Cleaning means for cleaning the sensor;
Measuring means for measuring a measurement object serving as a reference by the sensor;
Determination means for determining whether or not the measurement value obtained by the measurement means is within a preset allowable range;
A sensor cleaning apparatus comprising: a control unit that alternately repeats the cleaning by the cleaning unit and the measurement by the measuring unit until the determination unit determines that the measured value is within a preset allowable range. In a measurement method that performs measurement using a sensor that outputs a signal in response to the measurement target,
A cleaning step of cleaning the sensor for a predetermined time;
A first measurement step of measuring a first measurement object serving as a reference by the sensor washed for a predetermined time;
A determination step of determining whether or not a measurement value for the first measurement object is within a preset allowable range;
Repeating the cleaning step to the determination step until the measurement value for the first measurement object falls within the allowable range;
A second measurement stage in which a second measurement object is measured by a sensor whose measurement value for the first measurement object is within the allowable range;
Obtaining a difference between a final measurement value obtained by the measurement for the first measurement object and a measurement value obtained by the measurement for the second measurement object as a characteristic value of the second measurement object. A measuring method characterized by the above. A sensor that outputs a signal in response to the measurement object;
Cleaning means for cleaning the sensor;
First measurement means for measuring a first measurement object serving as a reference by the sensor;
Determination means for determining whether or not the measurement value obtained by the first measurement means is within a preset allowable range;
A cleaning control unit that alternately repeats the cleaning by the cleaning unit and the measurement by the first measuring unit until the determination unit determines that the measured value is within a preset allowable range;
Reference value storage means for storing, as a reference value, a measurement value when it is determined by the determination means that the measurement value is within a preset allowable range;
Second measurement means for measuring a second measurement object by the sensor from which the measurement value within the allowable range is obtained for the first measurement object;
Measurement provided with characteristic value calculation means for calculating a difference between the measurement value obtained by the second measurement means and the reference value stored in the reference value storage means as the characteristic value of the second measurement object apparatus.

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