JPH11281570A - Sensor device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sensor device which can reduce a noise caused by a temperature fluctuation in the circumference by a simple constitution and by which a substance to be measured can be detected with high sensitivity. SOLUTION: While a measurement-related substance which is fed into pipes 51 to 53 is passed through sections by the pipes 51 to 53 whose outer circumferential part is surrounded by a temperature-change buffering mechanism composed of a container 1 whose outer circumferential part is covered with a heat insulating material and of a heating medium 3, its temperature becomes nearly equal to the temperature of the heating medium 3 due to heat exchange between itself and the heating medium 3. The measurement-related substance in this state reaches a sensor chip 11 as the detecting surface of a surface plasmon sensor. The measurement-related substance in which thermal fluctuation received from a solution storage part, from pipes 53 , 55 , 56 , from a pump and from the like (especially from heat generated in the moving part of the pump) is nearly canceled by the temperature-change buffering mechanism is fed to the surface plasmon sensor, a substance, to be measured, whose temperature is nearly constant can be detected.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention generally relates to a sensor device for detecting an object to be measured and outputting a predetermined signal.
In particular, the present invention relates to an improvement in a sensor device which is easily affected by temperature fluctuation in the field of biosensors utilizing an enzyme reaction such as an antigen-antibody reaction or a catalytic reaction. Hereinafter, a surface plasmon sensor using the surface plasmon resonance method will be described as an example.

[0002]

2. Description of the Related Art Since a surface plasmon sensor can measure the refractive index of a medium near the surface of a sensor element (hereinafter referred to as a sensor chip), it is used for a chemical sensor such as a gas sensor and a biosensor using an antigen-antibody reaction. . The above-described sensor has already been put to practical use as a biosensor for immobilizing an antibody on a sensor chip and detecting and quantifying proteins, nucleic acids, and other biological substances to which the antibody specifically binds.

[0003]

The surface plasmon sensor can detect a change in the refractive index of a substance to be measured with very high sensitivity, but also has a disadvantage that it is easily affected by ambient temperature fluctuations. I have. For example, when the substance to be measured is an aqueous solution, the refractive index of water, which is a solvent, changes depending on the temperature, thereby causing a change in the refractive index (fluctuation in the refractive index) of the aqueous solution as a whole due to temperature,
This change in the refractive index becomes noise of the surface plasmon sensor.

Therefore, as means for reducing the noise caused by the temperature fluctuation in the surroundings, a method of accommodating the entire sensor device in a large-sized thermostatic bath capable of precisely controlling the temperature, a method of controlling the temperature of the substance to be measured by a temperature sensor, or the like. There has been proposed a method of measuring the temperature and correcting the output signal from the surface plasmon sensor using the measured temperature value.

Further, the following method has been proposed as another means. That is, when the substance to be measured is present in the solution as a solute, a plurality of sensor chips are prepared, and one of them is used for temperature monitoring.
The substance to be measured is detected by the remaining sensor chips. Then, the difference between the output signal from each sensor chip for detecting the target substance and the output signal from the sensor chip for monitoring the temperature is used as the output signal of the target substance from which noise due to temperature has been removed. Etc. have been proposed.

For example, when the substance to be measured is an antigen present as a solvent in a solution and a surface plasmon sensor is used as a sensor chip, two sensor chips are prepared, and one of them has a non-surface on the surface. A thin film for preventing specific adsorption is provided, and an antibody that specifically reacts with an antigen to be measured is immobilized on the other surface. In this state, the refractive index of the solution is measured by a sensor chip having a thin film for preventing non-specific adsorption, whereby the sensor chip functions as a temperature monitor. On the other hand, the above antigen as a measurement target substance is detected by a sensor chip on which an antibody is immobilized. Then, the difference between this output signal and the output signal from the temperature monitor becomes a detection signal of the measurement target substance from which noise due to temperature has been removed.

However, in each of the above-described methods, when the entire sensor device is housed in a large-sized and constant temperature bath capable of precisely controlling the temperature, not only a large installation space is required but also a very expensive method is required. There is a problem that is. Next, in the case of the method of correcting the output signal from the surface plasmon sensor using the measured temperature value of the measurement target substance, since the measurement target substance is usually a very small amount, the temperature of the measurement target substance depends on the temperature of the temperature sensor itself. There is a problem that the temperature can be changed. Further, in the case where one of the two surface plasmon sensors is used for temperature monitoring and the substance to be measured is detected by another sensor chip, there is a problem that the cost is high and the device space is large.

Accordingly, an object of the present invention is to reduce noise caused by ambient temperature fluctuation with a simple configuration,
An object of the present invention is to provide a sensor device capable of performing highly sensitive detection.

[0009]

A sensor device according to the present invention comprises: a sensor element for detecting a substance to be measured and outputting a predetermined signal; and a measurement device located upstream of the sensor element in the moving direction of the substance to be measured. Means for buffering temperature fluctuations of the target substance.

According to the above configuration, since the detection by the sensor element is performed after the temperature of the substance to be measured is adjusted to the temperature of the temperature fluctuation buffer means, noise caused by temperature fluctuation is reduced from the output signal of the sensor device. can do.

In a preferred embodiment according to the present invention, the sensor device includes at least one or more first introduction passages for penetrating the temperature fluctuation buffer means and leading a measurement-related substance including a substance to be measured. A second introduction path that communicates with the first introduction path and guides the measurement-related substance that has passed through the first introduction path to the detection surface of the sensor element. The measurement-related substance includes a measurement target substance, a measurement auxiliary substance necessary for measurement of the measurement target substance, and a purification substance for removing the measurement target substance attached to the detection surface of the sensor element. A plurality of roads are provided so as to be able to individually supply the measurement target substance, the measurement auxiliary substance, and the purification substance.

According to the above configuration, each measurement-related substance passes through a different first introduction path, so that each measurement-related substance remains in the section of the first introduction path existing in the temperature fluctuation buffer means.
Therefore, the temperature of each measurement-related substance is automatically adjusted to the temperature of the temperature fluctuation buffer. In addition, since the first introduction path is provided for each measurement-related substance, each measurement-related substance can be sent to the sensor element in a short time.

[0013] In the above embodiment, the sensor element is integrally attached to the temperature fluctuation buffer means, and the second introduction path is provided in the temperature fluctuation buffer means. By providing the second introduction path in the temperature fluctuation buffer, the temperature of each measurement-related substance sent to the detection surface of the sensor element is substantially equal to the temperature of the temperature fluctuation buffer. Therefore, temperature fluctuation of each measurement-related substance hardly occurs on the detection surface of the sensor element.

In a modification of the above embodiment, the sensor element is detachably attached to the temperature fluctuation buffer means,
The second introduction path is provided in the temperature fluctuation buffer means. Since the sensor element is detachable from the temperature fluctuation buffering means, the sensor element can be easily transported or replaced with a new one.

Further, in the above-mentioned modified example, in a state where the second introduction path and the sensor element are covered with the temperature fluctuation buffering means,
Attached to temperature fluctuation buffer means. By covering the second introduction path and the sensor element with the temperature fluctuation buffer means, it is possible to make the temperature of the second introduction path and the sensor element substantially equal to the temperature of the heat medium in the temperature fluctuation buffer means. Therefore,
It is possible to suppress temperature fluctuation of the measurement-related substance sent to the sensor element via the second introduction path.

In the above embodiment, the sensor element is any one of a surface plasmon sensor using a surface plasmon resonance method, a crystal oscillator sensor using a crystal oscillator, and an enzyme sensor.

The temperature fluctuation buffer means comprises a container whose outer peripheral portion is covered with a heat insulating material, and a heat medium contained in the container. The temperature fluctuation buffer unit has at least one or more measurement-related substance storage units. By having a measurement-related substance storage unit, it is possible to store more measurement-related substances than necessary for one sensor output while the temperature of the measurement-related substance and the temperature of the heat medium are substantially equal. it can.

In the above embodiment, any one of a liquid, a metal, and a gel-like substance obtained by adding water to a water-soluble polymer is used as the heat medium.

In another modification of the above embodiment, there is provided a temperature detecting means for detecting the temperature of the heat medium and outputting a signal for correcting the output signal of the sensor element. According to this configuration, a problem in which the temperature of the measurement target substance fluctuates due to the temperature of the temperature detection unit is less likely to occur.

Further, in another modified example of the above embodiment, there is further provided a means for heating the temperature of the heat medium to a predetermined temperature.

[0021]

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

FIG. 1 is a cross-sectional view showing the entire configuration of the sensor device according to the first embodiment of the present invention, as viewed from the side.

As shown in FIG. 1, the sensor device includes a container 1, a heat medium 3, a plurality of pipes 51 to 56, a storage tank 7, a prism 9, a sensor chip 11, a light source 1
5, a light receiving element 17, and a lens 19. Container 1
, The heat medium 3, the pipes 51 to 56, and the storage tank 7 constitute a temperature fluctuation buffer mechanism which will be described in detail below.
, Sensor chip 11, light source 15, light receiving element 17
And the lens 19 constitute a surface plasmon sensor.

The container 1 houses the heat medium 3 therein, and its outer peripheral portion is covered with a heat insulating material (not shown). As shown in FIG. Each has a circular hole for penetrating the pipe 53, and a circular hole for penetrating the pipe 54 in a member constituting the side surface thereof. Further, the container 1 has circular holes through which the converging pipes 55, pipes 53 and 54 of the pipes 51 and 52 penetrate the members constituting the lower surface thereof, and pipes 55 extending horizontally along the lower surface. The pipes 53 and 54 communicate with each other, and
It has a pipe 56 whose lower part is open and is integrally connected to the sensor chip 11 in a liquid-tight manner.

The pipes 51 to 53, 55 are for introducing measurement-related substances (general term including the above-mentioned substances to be measured, measurement auxiliary substances, and purification substances, which will be described in detail later) into the pipe 56. The pipe 56 is for guiding the measurement-related substance provided through the pipes 51 to 53 and 55 to the surface of the sensor chip 11. At the bottom of the pipe 56, a sensor chip 1
1 is attached by, for example, an adhesive or the like, and is fixed in a liquid-tight state. The pipe 54 is connected to the pipe 56 through the pipes 51 to 53.
Various solutions as measurement-related substances which are introduced into the inside and move along the surface of the sensor chip 11 are discharged from the inside of the pipe 56 to the outside. In the present embodiment, the storage tank 7 is connected to the pipe 53 so that the capacity required for measuring the measurement auxiliary substance among the measurement-related substances at least once can be stored in the container 1. An upstream side of the pipes 51 to 53 is connected to a pumping means such as a pump (not shown) and a solution storage unit (not shown) for storing a solution as a measurement-related substance.

The sensor chip 11 constitutes a sensor chip unit together with the prism 9 and is provided so as to be joined to the surface of the prism 9. The lens 19 is a light source 1
By condensing the light emitted from 5 on the surface of the sensor chip 11, surface plasmon resonance is excited in the sensor chip 11. Light receiving sensor (photodetector) 17
Receives reflected light from the sensor chip unit,
A signal reflecting the intensity distribution of the reflected light in the sensor chip unit is output. Based on this signal, an arithmetic processing unit (not shown) such as a microcomputer calculates the resonance angle of surface plasmon resonance. Thereby, the refractive index of the substance to be measured is determined.

FIG. 2 is a sectional view of a storage tank provided in the sensor device shown in FIG.

As shown, the storage tank 7 is formed in a horizontal direction, and has a configuration in which the inside is divided into an upper tank 25 and a lower tank 27 by a partition wall 23 having a through hole 21 in the center. . In the present embodiment, in order to increase the contact area between the storage tank 7 and the heating medium 3, for example, a plurality of fins (not shown) are provided on the inner wall surface and the outer wall surface of the storage tank 7, respectively. And

In the storage tank 7 having the above configuration, a measurement-related substance (measurement auxiliary substance) at a constant temperature in the upper tank 25.
Flows into the lower tank 27 through the through-hole 21, thereby extruding a measurement auxiliary substance at a constant temperature in the lower tank 27 to the pipe 53. As a result, a measurement auxiliary substance having a constant temperature without temperature fluctuation, that is, a measurement auxiliary substance having substantially the same temperature as the heat medium 3 is supplied from the storage tank 7 to the surface of the sensor chip 11 through the pipe 53.

In this embodiment, the container 1 has a length of about 50
An acrylic resin material having a thickness of about 100 mm, a width direction of about 100 mm, a height direction of about 150 mm, and a thickness of about 2 mm is used, and styrene foam is used as a heat insulating material (not shown) for covering the outer peripheral portion of the container 1. As the heating medium 3, a liquid heating medium, for example, tap water is used. Piping 51
The plurality of holes through which through 54 pass are sealed by a sealing material such as silicone rubber, for example, to prevent the heat medium 3 in a liquid phase such as tap water from leaking out of the container 1 from each hole. In addition, PEEK resin tubes having an outer diameter of 1/16 inch and an inner diameter of 1 mm are used for the pipes 51 to 54, respectively, and the pipe 53 is connected to the pipe 53 so that auxiliary substances necessary for one or more measurements can be stored in the container 1. The above-mentioned storage tank 7 is connected. Furthermore, in the present embodiment, a gold thin film is used for the sensor chip 11, and a dextran gel thin film layer is provided on the surface of the gold thin film so as to prevent fine particles such as dust in the buffer solution from adsorbing to the thin gold film.

In this embodiment, as the above-mentioned measurement-related substances, a measurement auxiliary substance such as a buffer, a measurement target substance such as a sample, and a purifying substance such as a dissociation liquid are used. The buffer determines a reference value (base line) for measurement performed by the sensor device according to the present embodiment, and is guided to the surface of the sensor chip 11 through the pipe 53, the storage tank 7, and the pipe 56. The sample is an object to be measured by the sensor device according to the present embodiment, that is, a substance to be measured, and is guided to the surface of the sensor chip 11 through the pipes 51, 55, and 56. The dissociation liquid is a substance for returning the sensor chip 11 to a state before measurement by dissociating a sample (substance to be measured) adsorbed on the surface of the sensor chip 11 from the surface of the sensor chip 11, and the pipes 52, 55, 56 Through the sensor chip 11.

The procedure of the measurement is as follows. First, with a plurality of antibodies corresponding to the antigen as the measurement target adhered to the surface of the sensor chip 11, a buffer solution is added to the pipe 53,
It flows toward the surface of the sensor chip 11 through the storage tank 7 and the pipe 56. At this time, as the signal reflecting the intensity distribution of the reflected light in the sensor unit, a signal as shown by the curve a in FIG. 3, that is, a signal having a minimum reflectance at the reflection angle θ1 is output from the light receiving element 17. Is done. The value of the reflection angle θ1 shown in FIG. 3 is a reference value for measurement. Next, a sample solution (that is, a solution containing the sample (antigen as a target)) is supplied to the pipes 51, 55, 5
Flow through 6 toward the surface of the sensor chip 11. As a result, some antigens in the sample solution adhere to the plurality of antibodies described above, and the remaining antigens float in the solution. Of the above antigens, the antigens floating in the solution are unnecessary, so in order to remove them, the buffer solution is again directed to the surface of the sensor chip 11 through the pipe 53, the storage tank 7, and the pipe 56. Shed. As a result, only the floating antigen is discharged to the outside through the pipe 54 using the buffer solution together with the sample solution. At this time,
From the light receiving element 17, a signal as shown by a curve b in FIG. 4, that is, a signal having a minimum reflectance at the reflection angle θ2 is output as a signal reflecting the intensity distribution of the reflected light in the sensor unit. The difference Δθ (= θ2−θ1) between the reflection angle θ2 and the reflection angle θ1 is a variation of the reflection angle due to the antibody-antigen reaction, and the Δθ indicates the antigen concentration. Δθ is given to the arithmetic processing device as an output from the sensor device, and the arithmetic processing device performs predetermined arithmetic processing, whereby the amount of protein actually contained in the sample can be quantified. After the above measurement is completed, the dissociation solution is sent through the pipes 52, 55, 56 to dissociate the antigen adhering to the antibody from the antibody and wash it off the surface of the sensor chip 11,
To the state before measurement. At the time of measurement, the above operation is repeated.

In the above configuration, each measurement-related substance sent at a predetermined timing to each of the pipes 51 to 53 by a pump or the like (not shown) is connected to the pipes 51 to 53 (surrounded by the temperature fluctuation buffer mechanism). Storage tank 7
), The temperature becomes substantially equal to the temperature of the heat medium 3 due to heat exchange with the heat medium 3. Then, it directly flows into the pipe 56 and reaches the sensor chip 11 which is the detection surface of the surface plasmon sensor. for that reason,
On the surface of the sensor chip 11, a solution storage section and a pipe 51 are provided.
~ 53,55,56, and related substances whose thermal fluctuations received from pumps etc. (especially heat generation in the movable parts of the pumps) are almost canceled by the above temperature fluctuation buffer mechanism, and are almost constant in the surface plasmon sensor. A substance whose temperature is to be measured can be detected. That is, the temperature fluctuation of the substance to be measured can be removed only by providing a container whose outer peripheral portion is covered with a heat insulating material and a relatively inexpensive temperature fluctuation buffer mechanism made of a heating medium such as tap water.

Therefore, in order to remove the temperature fluctuation of the substance to be measured, not only the surface plasmon sensor but also the solution storage unit, the piping, the pump and the like are large and 1/100 ° C.
Since it is not necessary to house in a very high-cost thermostat that performs the following high-precision temperature control, the cost does not increase.

Further, unlike the method of providing a temperature sensor for detecting the temperature of the substance to be measured in addition to the surface plasmon sensor and correcting the output signal from the surface plasmon sensor, when the temperature sensor is brought into contact with the substance to be measured. It is not necessary to consider the influence of the temperature of the temperature sensor itself on the target substance (temperature fluctuation).

Further, unlike the method of providing a surface plasmon sensor for monitoring the temperature of the substance to be measured in addition to the surface plasmon sensor for detecting the substance to be measured, it is not necessary to consider a cost increase due to an increase in the space of the apparatus. I can do it.

In this embodiment, the storage tank 7 is connected to the pipe 53 as a means for storing an amount of buffer solution that can be measured one or more times in the container 1. In the present embodiment, the configuration in which the storage tank is provided is not particularly shown for the pipe 51 for passing the sample and the pipe 52 for passing the dissociation solution, but it is naturally possible to provide the storage tank also for these. In addition, instead of the storage tank 7 and the like, a pipe (51, 52, 5,
3) It is also possible to adopt a method of increasing the length.

FIG. 5 is a diagram showing the results of measurement by a surface plasmon sensor when a phosphate buffer solution containing a surfactant of pH 6.8 was used as a substance to be measured.

In FIG. 5, a curve (thick curve)
Hears an output signal from the surface plasmon sensor for 30 minutes when the above-mentioned substance to be measured is sent to the surface plasmon sensor chip at a flow rate of 500 microliters per minute using the sensor device having the above-described temperature fluctuation buffer mechanism. Shows the data recorded over the range. On the other hand, the curve (the thinner curve) shows the surface plasmon when the above-mentioned substance to be measured was sent to the surface plasmon sensor chip at a flow rate of 500 microliters per minute using a sensor device having no temperature fluctuation buffer mechanism. 3 output signals from the sensor
The data recorded over 0 minutes is shown.

Comparing and comparing the above curves, the reproducibility of repeatedly measuring the same substance to be measured is better when using a sensor device having a structure in which a temperature fluctuation buffer mechanism is provided in front of the sensor chip of the surface plasmon sensor. It is apparent that the temperature is considerably higher than when a sensor device having no temperature fluctuation buffer mechanism is used. This means that noise caused by the temperature of the substance to be measured could be reduced by the temperature fluctuation buffer mechanism.

FIG. 6 is a cross-sectional side view showing the entire configuration of a sensor device according to a second embodiment of the present invention.

In the present embodiment, a sensor unit is formed by the sensor chip unit (consisting of the prism 9 and the sensor chip 11 as described above) and the sensor cell 13, and this sensor unit is provided in the container 1. Its main feature is that it is detachable.

That is, in this embodiment, the sensor chip 11
A sensor cell 13 is provided on the sensor chip 11 in order to protect the surface of the container 1. The sensor unit is detachably attached to the lower surface of the container 1 via the sensor cell 13. In the members constituting the lower surface of the container 1, through holes are provided corresponding to the pipes 53, 55, 54, respectively. Inside the sensor cell 13, pipes 51 to 53, 55
The pipe 56 is provided in the above-described manner in order to introduce the measurement-related substance given through the sensor chip 11 into the surface of the sensor chip 11. The lower portion of the pipe 56 is open, and the sensor chip 11 is integrally connected to the open portion in a liquid-tight manner. Sensor chip 11 inside piping 56
The measurement-related substance moving along the surface of the sensor cell 13 is discharged out of the sensor cell 13 through the pipe 54.

The reason for configuring the sensor unit as described above is as follows.

That is, in the surface plasmon sensor, the protection state and the storage state of the sensor element greatly affect the sensor output. Further, in the surface plasmon sensor, it is necessary to replace the sensor element with a new one in accordance with the use state and the use period of the sensor element in order to stably obtain a good sensor output. Therefore, in the present embodiment, the sensor cell 13 having the pipe 56 inside is provided on the surface of the sensor chip 11 as described above. Thereby, the sensor chip 1
The surface of the sensor chip 11 can always be stored in a measurable state by protecting the surface of the sensor chip 11 and storing the pipe 56 filled with a storage solution. Further, unlike the sensor device shown in FIG. 1, the sensor unit can be removed from the container 1 and only the sensor unit can be replaced with a new one, so that the replacement operation can be easily performed and the entire device including the container 1 can be replaced. It is also possible to significantly reduce the cost as compared with the case of replacing with a new one.

FIG. 7 is a cross-sectional view showing the entire configuration of the sensor device according to the third embodiment of the present invention, as viewed from the side.

In the present embodiment, the above-mentioned solution storage sections (for separately storing measurement-related substances such as a buffer solution, a sample, and a dissociation solution) are denoted by reference numerals 291, 292, and 293, respectively. In the solution reservoir 2
The main feature is that the temperatures of the measurement-related substances in 91, 292, and 293 are made substantially equal to the temperature of the heat medium 3.

According to the above configuration, the solution storage sections 291-2
Each measurement-related substance in 93 is sent into each of the pipes 51 to 53 in the heating medium 3 by a pumping means (not shown) such as a pump. For this reason, the temperature difference between the temperature of each measurement-related substance and the heat medium 3 during storage is very small as compared with an apparatus that does not have a solution storage section in the container 1.
During the passage through, the temperature fluctuation of each measurement-related substance can be buffered in a shorter time than in a device having no solution storage section in the container 1.

FIG. 8 is a side sectional view showing the entire configuration of a sensor device according to a modification of the third embodiment of the present invention.

In the present embodiment, in the container 1 having the structure shown in FIG. 7, the sensor unit is detachably attached to the container 1 while at least a portion from the sensor cell 13 to the sensor chip 11 is immersed inside the container 1. The main feature is that it is formed so that it can be attached.

That is, a concave portion is formed on the lower surface of the housing portion of the heat medium 3 in the container 1 so that the portion from the sensor cell 13 to the sensor chip 11 can be attached in a state of being immersed,
A sensor unit is detachably attached to the concave portion in a liquid-tight state. Other configurations are the same as those shown in FIG.

According to the above configuration, the portion from the sensor cell 13 to the sensor chip 11 is held in a state of being immersed below the housing portion of the heat medium 3 in the container 1, so that the temperature of the sensor unit itself is reduced by the heat catalyst. The temperature can be made substantially equal to the temperature of (3). Therefore, the influence of the temperature on each measurement-related substance sent to the sensor chip 11 through the pipe 56 in the sensor cell 13 from the sensor unit is applied to an apparatus in which a portion extending to the sensor cell 13 and the sensor chip 11 is located outside the container 1. Thus, the temperature fluctuation buffer effect of each measurement-related substance can be improved.

FIG. 9 is a side sectional view showing the entire configuration of a sensor device according to a fourth embodiment of the present invention.

In the sensor device according to the present embodiment, in order to measure the temperature of the measurement-related substance in addition to the surface plasmon sensor having the structure shown in FIG. The main feature is that a temperature sensor 31 inserted therein is provided. That is, in the above sensor device, the temperature of the substance to be measured is measured by the temperature sensor 31, and the output signal of the sensor element is obtained from the measured value and the temperature characteristic of the sensor element (surface plasmon sensor) known in advance.
For example, the correction is made by an arithmetic processing means such as a microcomputer.

In FIG. 9, while the measurement-related substances sent into the pipes 51 to 53 pass through the sections of the pipes 51 to 53 whose outer periphery is surrounded by the temperature fluctuation buffer mechanism, the heating medium 3 , The temperature of the heat medium 3 to be measured by the temperature sensor 31 becomes substantially equal to the temperature of the heat medium 3. That is, by measuring the temperature of the heat medium 3, the temperature of the substance to be measured can be measured.

According to the present embodiment, the output signal of the sensor element is corrected based on the measured temperature of the substance to be measured and the temperature characteristic of the sensor element which is known in advance.
Fluctuation due to temperature can be more reliably removed from the measurement result by the surface plasmon sensor. In the present embodiment, since a small amount of the target substance is not directly measured by the temperature sensor 31, there is no possibility that the temperature of the target substance fluctuates due to the temperature of the temperature sensor 31 itself.

FIG. 10 is a side sectional view showing the overall configuration of a sensor device according to a modification of the fourth embodiment of the present invention.

In the sensor device according to this modification, in addition to the configuration shown in FIG. 9, a Peltier element 33, which is a thermoelectric semiconductor, is attached to the wall surface of the container 1 while being in contact with the heat medium 3. Is the main feature. This Peltier device 33
Is known as an element having a function of generating heat on one side by supplying power and absorbing heat on the opposite side.

In the above configuration, the temperature of the heat medium 3 is controlled to a predetermined temperature by supplying electric power to the Peltier element 33 while measuring the temperature of the heat medium 3 by the temperature sensor 31. As this control method, for example, PID (proportional,
Integral, derivative) control is adopted. After the heat medium 3 is controlled to a predetermined temperature in this manner, the temperature fluctuation (noise caused by heat) of the measurement-related substance can be removed, as in the above-described embodiments, whereby the measurement target can be removed. A more accurate refractive index measurement of a substance can be performed.

The above description relates only to each embodiment of the present invention, and does not mean that the present invention is limited to only the above described contents. For example, in each of the embodiments described above, tap water is used as the heat medium 3. However, the heat medium 3 is not limited to tap water, and water containing an antifreeze or a germicide, or distilled water, Needless to say, ultrapure water may be used. By using these liquids, it is possible to prevent freezing and corrosion that can occur in tap water. Further, other than water, a solid such as a metal or a liquid other than water may be used as the heat medium 3.

As the heat medium 3, a gel-like substance typified by a water-soluble polymer containing water can also be used. This gel-like substance is easier to handle than a liquid and has a larger heat capacity, and therefore is more suitable for the heat medium 3 than the water described above.

In each of the above-described embodiments, the surface plasmon sensor has been described as an example of the sensor element. However, the sensor element according to the present invention is not limited to the surface plasmon sensor, but may be a quartz oscillator sensor or an enzyme sensor. Naturally, it can be applied to various sensors such as sensors which are easily affected by temperature.

The sections of the pipes 51 to 53 passing through the temperature fluctuation buffer mechanism need not be linear as shown in FIGS. 1 and 6 to 10, and the substances to be measured pass through the temperature fluctuation buffer mechanism. In order to increase the time required for measurement (to increase the amount of measurement-related substances stored in the temperature fluctuation buffer mechanism),
It may be spiral or bent.

Further, as the heat insulating material covering the outer peripheral portion of the container 1, a material having a low thermal conductivity such as a resin sponge sheet or other material used for a buffer may be used instead of styrene foam. .

Further, by adjusting the shape of the connecting portion between the pipes 55 and 53 and the pipe 56, it is possible to adjust the mixing ratio of each measurement-related substance. For example, the sample is mixed with a buffer when measuring, and adjusted to a concentration that can be measured by a surface plasmon sensor. By adjusting the inner diameter of the pipe 51 and the inner diameter of the pipe 53 to dimensions calculated from the mixing ratio, The sample and the buffer are transferred to the sensor chip 11
It is possible to adjust the concentration simply by feeding the surface.

[0066]

As described above, according to the present invention,
It is possible to provide a sensor device that can reduce noise due to ambient temperature fluctuations with a simple configuration and can perform highly sensitive detection.

[Brief description of the drawings]

FIG. 1 is a cross-sectional view showing the entire configuration of a sensor device according to a first embodiment of the present invention, as viewed from a side.

FIG. 2 is a sectional view of a storage tank provided in the sensor device of FIG. 1;

FIG. 3 is a diagram showing an output signal from a light receiving element.

FIG. 4 is a diagram showing an output signal from a light receiving element.

FIG. 5 is a comparative chart of a measurement result by a surface plasmon sensor when a phosphate buffer solution containing a surfactant of PH 6.8 is used as a substance to be measured.

FIG. 6 is a side cross-sectional view showing the entire configuration of a sensor device according to a second embodiment of the present invention.

FIG. 7 is a cross-sectional view showing the entire configuration of a sensor device according to a third embodiment of the present invention, as viewed from a side.

FIG. 8 is a side cross-sectional view showing the overall configuration of a sensor device according to a modification of the third embodiment of the present invention.

FIG. 9 is a side cross-sectional view showing the entire configuration of a sensor device according to a fourth embodiment of the present invention.

FIG. 10 is a side cross-sectional view showing the entire configuration of a sensor device according to a modification of the fourth embodiment of the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 Container 3 Heat medium 51,52,53,54,55,56 Pipe 7 Storage tank 9 Prism 11 Sensor chip 13 Sensor cell 15 Light source 17 Light receiving element 19 Lens (lens for condensing surface plasmon excitation light) 21 Through hole 23 Partition wall 25 Upper tank 27 Lower tank 291-293 Solution reservoir 31 Temperature sensor 33 Peltier element

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yumi Osaki 2-1-1 Nakajima, Kokurakita-ku, Kitakyushu-shi, Fukuoka Totoki Equipment Co., Ltd. 2-1-1, Totoki Kiki Co., Ltd.

Claims (13)

[Claims] 1. A sensor element for detecting a substance to be measured and outputting a predetermined signal, and buffering a temperature fluctuation of the substance to be measured, which is located upstream of the sensor element in a moving direction of the substance to be measured. And a sensor device. 2. The sensor device according to claim 1, wherein at least one or more first introduction paths penetrating through the temperature fluctuation buffer means and leading a measurement-related substance including the substance to be measured, and A second introduction path communicating with the first introduction path and guiding the measurement-related substance that has passed through the first introduction path to a detection surface of the sensor element. 3. The sensor device according to claim 1, wherein the measurement-related substance is the measurement target substance, a measurement auxiliary substance necessary for measuring the measurement target substance, and a detection surface of the sensor element. And a purifying substance for removing the substance to be measured attached to the specimen, wherein the first introduction path is provided in plural numbers so that the substance to be measured, the auxiliary measuring substance, and the purifying substance can be individually supplied. A sensor device, characterized in that: 4. The sensor device according to claim 1, wherein said sensor element is integrally attached to said temperature fluctuation buffer means. 5. The sensor device according to claim 1, wherein the sensor element is detachably attached to the temperature fluctuation buffer. 6. The sensor device according to claim 4, wherein the second introduction path is provided in the temperature fluctuation buffer unit. 7. The sensor device according to claim 5, wherein the sensor element is configured such that at least a portion where the second introduction path is provided is covered with the temperature fluctuation buffer unit. A sensor device which is attached to temperature fluctuation buffer means. 8. The sensor device according to claim 1, wherein the sensor element is one of a surface plasmon sensor using a surface plasmon resonance method, a crystal oscillator sensor using a crystal oscillator, and an enzyme sensor. A sensor device characterized by that. 9. The sensor according to claim 1, wherein the temperature fluctuation buffering means comprises a container whose outer peripheral portion is covered with a heat insulating material, and a heat medium contained in the container. apparatus. 10. The sensor device according to claim 9, wherein the temperature fluctuation buffer unit has at least one or more measurement-related substance storage units. 11. The sensor device according to claim 9, wherein the heat medium is one of a liquid, a metal, and a gel-like substance obtained by adding water to a water-soluble polymer. Sensor device. 12. The sensor device according to claim 9, further comprising a temperature detection unit that detects a temperature of the heat medium and outputs a signal for correcting an output signal of the sensor element. apparatus. 13. The sensor device according to claim 9, further comprising means for heating the temperature of the heat medium to a predetermined temperature.