JP5491111B2 - Micro sensing device - Google Patents

Description

  The present invention relates to a micro-sensing device that resonates a crystal resonator and performs physical quantity measurement and analysis of a measurement object from the resonance change.

Conventionally, quartz resonators have been used in many frequency standards for electronic circuits incorporated in various electronic devices such as watches, computers, and measuring devices, and are used as highly accurate and stable oscillation elements.
In recent years, an apparatus has been developed that uses this crystal resonator to analyze the characteristics of an object to be measured and to measure physical quantities (such as viscosity). This apparatus mainly uses a quartz vibrator that vibrates in thickness. Electrodes to which a voltage is applied are formed on both sides of the crystal resonator, and after applying the voltage, the crystal resonator resonates at a predetermined frequency by an oscillation circuit. At this time, the crystal resonator is disposed so that at least one of the electrodes is in contact with the measurement object introduced into the reaction vessel.

  In such a configuration, for example, when a measurement target is a specific substance (for example, an antibody or a protein) and the characteristics of the specific substance are analyzed, the specific substance is first adsorbed on the surface of the crystal unit. A predetermined amount of a fixed substance called a ligand or the like that binds by reaction is fixed. Thereafter, a solution containing a specific substance is introduced into the reaction tank, and the crystal resonator is resonated. Then, since the specific substance is adsorbed and bound to the fixed substance, a minute mass change occurs near the surface of the crystal unit. As a result, the resonance frequency of the crystal resonator changes. That is, a minute mass change can be measured as a resonance frequency change. Subsequently, the above measurement is performed for each of solutions containing a plurality of specific substances. And the adsorption constant which adsorb | sucks to a fixed substance is computable from those measurement results.

On the other hand, even when the specific substance is desorbed from the fixed substance, a minute mass change occurs in the vicinity of the surface of the crystal oscillator, so that the resonance frequency of the crystal oscillator changes. Therefore, as in the case described above, the desorption constant desorbed from the fixed substance can be calculated.
Thus, the desorption adsorption constant of the specific substance with respect to the fixed substance can be obtained, and the characteristics of the specific substance can be analyzed. In particular, this method can be applied to new drug development and the like, and is expected in fields such as biochemistry and biotechnology.

Further, when the object to be measured is a liquid and the viscosity (physical quantity) of the liquid is measured, first, the reference solution is introduced into the reaction tank and the crystal resonator is resonated. Then, the resonance resistance value at the resonance point, that is, the reference resistance value is measured in advance.
Next, a liquid to be measured is introduced into the reaction tank, and the crystal resonator is resonated. At this time, the crystal resonator receives a resistance corresponding to the viscosity from the liquid, so that the resonance resistance changes. And the measurement data which compared the resonance resistance value measured here and the reference | standard resistance value measured previously are acquired. Subsequently, the same measurement is performed for a plurality of different reference solutions, and measurement data for each reference solution is acquired. And based on the calibration curve of these several measurement data, the viscosity of the liquid to measure can be measured.

  As described above, a technique for analyzing an object to be measured and measuring a physical quantity based on a resonance change of a crystal resonator is known. However, since a crystal resonator has a temperature characteristic, resonance vibration is caused by temperature. It will be affected. Therefore, in order to perform accurate measurement, it is desired to keep the temperature of the crystal resonator as constant as possible and suppress the change in the resonance frequency and the change in the resonance resistance value caused by the temperature change.

  In addition, the reaction in which a specific substance adsorbs and desorbs on a fixed substance is also easily affected by temperature changes. Therefore, when this reaction is performed, it is more strongly required to keep the temperature of the crystal resonator constant.

In order to meet such needs, at least one of a cell and an oscillation circuit is embedded in a metal block such as an aluminum block to which a heating means such as a heater or a cooling means such as a Peltier cooling element is attached. An apparatus that performs measurement in a state in which the temperature of the metal block is temperature-controlled is known (see Patent Document 1).
According to the apparatus configured as described above, since the crystal resonator disposed in the cell can be controlled to a predetermined temperature, accurate measurement can be performed.

JP-A-10-38784

However, in the conventional apparatus, whether the oscillation circuit is embedded in the metal block together with the cell and is temperature-controlled together, or disposed separately from the metal block and not temperature-controlled at all. It is in either state.
In general, an electric element constituting an oscillation circuit easily generates heat, and the temperature inevitably rises during operation of the oscillation circuit. For this reason, the temperature of the electric element is several to several tens of degrees higher than the temperature at which the oscillation circuit is placed. Therefore, when the temperature of the oscillation circuit is not controlled at all, the temperature of the electric element becomes too high during the measurement, and the electric element cannot withstand this temperature, and there is a fear that the electric element breaks down.
Even if the oscillation circuit is temperature controlled at the same time as the cell, if the temperature required for the measurement is high, the temperature of the crystal resonator must be set high. In such a case, the oscillation circuit itself becomes similarly high, and the temperature of the electric element becomes even higher than that. Therefore, there is a possibility that the electric element may fail.

  Further, in the conventional apparatus, not only the oscillating circuit and the cell are embedded, but also a shielding effect that eliminates the external electromagnetic influence is required for the metal lump, so that the size tends to increase. Therefore, it becomes a large-scale device and it is difficult to reduce the size. In addition, since it is necessary to control the temperature of a large metal lump, a large-scale power supply circuit is required, and the amount of electricity consumed may be enormous.

  The present invention has been made in consideration of such circumstances, and its purpose is to perform high-precision measurement and analysis using a crystal resonator without incurring defects in the electric elements constituting the oscillation circuit. It is possible to provide a micro-sensing device that can be easily reduced in size and power consumption.

In order to achieve the above object, the present invention provides the following means.
(1) In the microsensing device according to the present invention, a cell having a reaction vessel into which a measurement object is introduced and a pair of electrodes to which a voltage is applied are formed on both surfaces, and at least one electrode is introduced into the reaction vessel. A crystal resonator disposed in the cell so as to be in contact with the measured object, an oscillation substrate having an oscillation circuit that resonates the crystal resonator, and a first heating / cooling that heats and cools the crystal resonator A second heating / cooling unit that heats and cools the oscillation circuit, a first temperature control unit that controls the temperature of the first heating / cooling unit, and a second that controls the temperature of the second heating / cooling unit. The temperature controller is provided.

  In the microsensing device according to the present invention, the measurement object is introduced into the reaction tank, and a voltage is applied to the pair of electrodes to resonate the crystal resonator by the oscillation circuit. Then, since the introduced measurement object acts on one side of the crystal unit including one electrode, the resonance frequency or the resonance resistance value of the crystal unit changes due to the influence. Therefore, by measuring the resonance change of such a crystal resonator, it is possible to measure a physical quantity such as the viscosity of the measurement object or to analyze the characteristics.

  By the way, when performing the above-described measurement and analysis, the crystal resonator can be appropriately heated and cooled using the first heating and cooling unit temperature-controlled by the first temperature control unit. It is possible to adjust to. Therefore, it is possible to suppress changes in the resonance frequency and resonance resistance value of the crystal resonator due to temperature changes. Therefore, highly accurate measurement and analysis can be performed. In addition, since the temperature of the crystal unit can be set to an optimum temperature according to the measurement object, highly accurate measurement and analysis can be performed in this respect.

  Also, the oscillation circuit can be appropriately heated and cooled by using the second heating / cooling unit whose temperature is controlled by the second temperature control unit as in the case of the crystal resonator, so that the temperature of the oscillation circuit is adjusted to a constant temperature. It is possible. In addition, since the temperature can be controlled separately from the crystal resonator, the temperature of the oscillation circuit can be adjusted to a desired temperature without being influenced by the temperature of the crystal resonator. Therefore, it is possible to suppress the electrical elements constituting the oscillation circuit from becoming too high as in the prior art. Therefore, measurement and analysis can be performed without causing problems such as a failure, and a highly reliable apparatus can be obtained.

Further, unlike the conventional case where the temperature of a large metal lump is controlled, it is only necessary to locally control the temperature of the crystal unit and the oscillation circuit, so that the first heating / cooling unit and the second heating / cooling unit can be reduced in size. Can be easily achieved. Therefore, it is easy to reduce the size of the first temperature control unit and the second temperature control unit that control the temperature thereof. Therefore, the size of the entire apparatus can be reduced.
In addition, since the temperature of the first heating / cooling unit and the second heating / cooling unit which are reduced in size may be controlled, power saving can be achieved as compared with the conventional case. In addition, even if the calorific values of the crystal resonator and the oscillation circuit are different from each other, the temperature can be controlled separately, so that the temperature can be efficiently controlled with an optimum temperature gradient suitable for each. Therefore, power saving can be achieved also in this respect.

In addition, since the temperature of the crystal unit and the oscillation circuit can be controlled separately, for example, the temperature of the crystal unit is controlled with high accuracy, and conversely, the temperature of the oscillation circuit is controlled with slightly low accuracy. It is also possible to make a difference. Accordingly, it is possible to narrow down the temperature control region with high accuracy, and it is possible to suppress an increase in cost. Therefore, it can also lead to cost reduction.
In addition, since the temperature of the crystal unit and the oscillation circuit can be controlled separately, even when the cell temperature is changed, the temperature of the oscillation circuit can be kept constant and affected by the temperature characteristics of the oscillation circuit. Therefore, the temperature characteristics can be accurately evaluated.

(2) The micro-sensing device according to the present invention is characterized in that, in the micro-sensing device according to the present invention, the first heating / cooling unit heats and cools the cell simultaneously with the crystal resonator.

  In the microsensing device according to the present invention, the first heating / cooling unit heats and cools the cell as well as the crystal unit. Thereby, it is possible to adjust to the temperature of a crystal oscillator also about the measuring object introduced into the reaction tank. The quartz resonator is easily influenced by the temperature of the measurement object having a larger heat capacity than itself. Therefore, even if only the crystal resonator is heated and cooled, it may be difficult to adjust to a desired constant temperature. However, by simultaneously heating and cooling the cells, the temperature of the crystal unit can be adjusted with higher accuracy without such a concern. Therefore, more accurate measurement and analysis can be performed.

(3) In the microsensing device according to the present invention, in the microsensing device according to the present invention, the second temperature control unit is configured such that the temperature of the oscillation circuit is within a range of + 5 ° C. or more and less than + 30 ° C. than room temperature. Thus, the temperature of the second heating / cooling unit is controlled.

  In the microsensing device according to the present invention, the temperature is controlled so that the temperature of the oscillation circuit becomes a temperature within the range of + 5 ° C. or more and less than + 30 ° C. from room temperature. The room temperature referred to here is a room temperature suitable for general experiments and measurements, and is an average room temperature for the year (approximately 25 ° C.). Usually, when measuring and analyzing a measurement object, it can be considered to be performed at room temperature. When the oscillation circuit is operated at such a room temperature, it naturally reaches a temperature that is naturally higher than the normal room temperature due to self-heating of the electric elements, and the temperature tends to settle down.

Therefore, by controlling the temperature of the oscillation circuit so as to be within the above-mentioned temperature range, it is possible to make the shape close to the natural state, and to control the oscillation circuit to a constant temperature without excessive heating and cooling. Can do. Therefore, it is easy to achieve further power saving.
If the temperature of the oscillation circuit is higher than 30 ° C. above room temperature, the electrical elements constituting the oscillation circuit are liable to malfunction, leading to a reduction in the life of the device and the energy consumption of the entire device. It becomes easy to invite increase.

(4) The micro-sensing device according to the present invention is the micro-sensing device according to the present invention, wherein the second temperature control unit is configured so that the temperature of the oscillation circuit is higher than a use environment temperature by a predetermined value after startup. As described above, the second heating / cooling unit is controlled to follow the change in the operating environment temperature, and after the measurement start is input, the second heating is performed so as to maintain the temperature reached at the time of the input. The temperature of the cooling unit is controlled.

  In the micro-sensing device according to the present invention, when the power is turned on and activated, the second temperature control unit causes the second heating / cooling unit so that the temperature of the oscillation circuit is a predetermined value higher than the use environment temperature. The temperature is controlled. At this time, when the use environment temperature changes due to air conditioning or the like after activation, the second temperature control unit controls the temperature of the second heating / cooling unit following the temperature change. Therefore, the temperature of the oscillation circuit is maintained at a temperature higher by a predetermined value than the use environment temperature. When the use environment temperature reaches the optimum temperature and measurement start is input, the second temperature control unit thereafter performs the second heating so as to maintain the temperature of the oscillation circuit that has been reached at the time of input. Control the temperature of the cooling section. For example, when the predetermined value is 15 ° C., when the use environment temperature reaches 25 ° C. (optimum temperature) and measurement start is input, the temperature of the oscillation circuit is maintained at 40 ° C. which has been reached at this time. Temperature control.

Normally, when the oscillation circuit is operated, the temperature naturally reaches a temperature higher than the use environment temperature due to self-heating of the electric element, and the temperature tends to settle down. Therefore, by controlling the temperature of the oscillation circuit so as to maintain a temperature higher than the operating environment temperature during measurement and analysis, it is possible to obtain a shape close to the natural state, and oscillation without excessive heating and cooling. The circuit can be controlled at a constant temperature. Therefore, it is easy to achieve further power saving.
In addition, since the temperature is controlled following the change in the operating environment temperature so that the temperature of the oscillation circuit is a predetermined value higher than the operating environment temperature after startup, the time lag is input after the start of measurement is input. It is possible to immediately measure and analyze the measurement object without generating any. Therefore, a device that is very easy to use and excellent in convenience can be obtained.

(5) In the micro-sensing device according to the present invention, in the micro-sensing device according to the present invention, the second temperature control unit has reached a temperature that is equal to or higher than a predetermined value determined in advance at the time of use. In this case, the temperature control is stopped.

  In the micro-sensing device according to the present invention, when the operating environment temperature reaches a predetermined value or more at the time of startup, the operating environment temperature is high (40 ° C. to 50 ° C.), for example, indoors in summer. If it has reached, the temperature control of the second heating / cooling section is stopped. Accordingly, it is possible to prevent the temperature of the oscillation circuit from reaching a temperature higher than a predetermined value by 40 ° C. to 50 ° C., and it is possible to prevent a problem from occurring due to this.

(6) The micro-sensing device according to the present invention is the micro-sensing device according to the present invention, wherein the second temperature control unit is configured such that the second heating / cooling is performed after the use environment temperature is lower than the specified value. The temperature control of the part is started.

  In the micro-sensing device according to the present invention, after the temperature control of the second heating / cooling unit is stopped, when the use environment temperature falls below a specified value due to air conditioning or the like, the second temperature control unit performs the second heating. Start cooling unit temperature control. As a result, the oscillation circuit can be operated more safely and the reliability can be improved.

(7) The micro-sensing device according to the present invention is the above-described micro-sensing device according to the present invention, wherein the insulating thermal conductive member disposed on both surfaces of the oscillation substrate and the oscillation via the thermal conductive member. A metal plate that clamps and fixes the substrate from both sides, and the second heating and cooling unit is fixed to the metal plate.

In the microsensing device according to the present invention, since the periphery of the oscillation substrate having the oscillation circuit is surrounded by the heat conductive member and the metal plate, the heat dissipation performance and the cooling performance are extremely excellent. Therefore, the temperature of the oscillation circuit can be quickly changed, the temperature can be adjusted to a desired temperature efficiently in a short time, and further power saving can be easily achieved.
In particular, since the second heating / cooling section is fixed to the metal plate, heat can be transmitted through the metal plate and the heat conductive member without wasting heat. Also in this respect, the above-described operational effects can be made remarkable.

  According to the micro-sensing device of the present invention, it is possible to perform high-precision measurement and analysis using a crystal resonator without causing defects in the electric elements constituting the oscillation circuit, and to reduce the size and power consumption. In addition, cost reduction can be achieved.

It is a block diagram of the microsensing device which concerns on this invention. It is a figure which shows the modification of the cell which comprises the microsensing apparatus shown in FIG.

  Hereinafter, embodiments of a microsensing device according to the present invention will be described. In the present embodiment, a case where the measurement object is a sample solution and the viscosity (physical quantity) of the sample solution is measured will be described as an example.

  As shown in FIG. 1, the micro-sensing device 1 according to the present embodiment includes a cell 2, a crystal resonator 3, an oscillation substrate 5 having an oscillation circuit 4, and a Peltier element that heats and cools the crystal resonator 3 (first Heating / cooling unit) 6, a temperature control unit (first temperature control unit) 7 that controls the temperature by supplying current to the Peltier device 6, and a Peltier device (second heating / cooling) that heats and cools the oscillation circuit 4. Part) 8 and a temperature control part (second temperature control part) 9 for controlling the temperature by supplying a current to the Peltier element 6.

  The cell 2 is composed of a base portion 2a and a cover portion 2b in which a reaction vessel 10 into which the sample liquid W is introduced is formed so as to cover the base portion 2a. The base portion 2a and the cover portion 2b are each formed of a metal material such as aluminum, and are combined in a state of being in close contact by fastening means such as screws (not shown).

A supply path 11 for supplying the sample liquid W from the outside and introducing it into the reaction tank 10 is formed in the cover portion 2b, and a discharge path for discharging the sample liquid W introduced into the reaction tank 10 to the outside. 12 is formed. At this time, the supply path 11 and the discharge path 12 are formed so as to face each other with the reaction tank 10 interposed therebetween. Therefore, when the sample liquid W supplied from the supply path 11 is discharged by the operation of a pump (not shown) or the like, the sample liquid W is surely passed through the reaction tank 10 and then discharged to the outside via the discharge path 12. Has been. Thus, the cell 2 of the present embodiment functions as a flow type cell that can be introduced into the reaction vessel 10 while flowing the sample liquid W.
A supply tube 13 and a discharge tube 14 are connected to the inlet of the supply channel 11 and the outlet of the discharge channel 12, respectively, so that the sample liquid W can be reliably supplied and discharged. Yes.

  The crystal unit 3 is, for example, an AT cut crystal piece, and is a transparent substrate formed in an approximately square shape from an 8 mm square wafer. A pair of electrodes to which a voltage is applied by a power source (not shown), that is, a detection electrode 20 and a counter electrode 21 are formed on both surfaces of the crystal unit 3. The detection electrode 20 and the counter electrode 21 are formed by vapor deposition, sputtering, or the like so as to be positioned substantially at the center of the crystal resonator 3. That is, the detection electrode 20 and the counter electrode 21 are in a state of facing each other with the crystal resonator 3 interposed therebetween. The crystal resonator 3 and the pair of electrodes 20 and 21 function as a QCM sensor.

  In addition, lead electrodes (not shown) that are electrically connected to the detection electrode 20 and the counter electrode 21 are formed on both surfaces of the crystal unit 3. These detection electrode 20, counter electrode 21 and lead electrode are formed by laminating one kind of metal or different metals (for example, laminating titanium and gold in two layers).

The thus configured quartz crystal resonator 3 is fixed on the base portion 2a so that the detection electrode 20 which is one of the electrodes is in contact with the sample liquid W introduced into the reaction vessel 10. At this time, O-rings 22 made of fluorine rubber, silicone rubber, or the like are fixed to both surfaces of the crystal unit 3. As a result, the sample liquid W is prevented from leaking to the counter electrode 21 side, and the counter electrode 21 is prevented from coming into direct contact with the base portion 2a.
The O-ring 22 on the detection electrode 20 side is fixed so as to be pressed from above by a fixing member 2 c formed on the inner surface of the cover portion 2 b of the cell 2.

Meanwhile, one surface of the Peltier element 6 is fixed to the lower surface of the base portion 2a of the cell 2 by adhesion or the like. A heat sink 26 to which a fan 25 is attached is fixed to the other surface of the Peltier element 6 (a surface opposite to the one surface).
The Peltier element 6 is connected to the temperature control unit 7, and one surface generates heat or absorbs heat by reversing the amount of current flowing from the temperature control unit 7 or polarity. In addition, the amount of heat generated and the amount of heat absorbed are also controlled. As a result, the Peltier element 6 can appropriately heat and cool the crystal unit 3 via the cell 2.
In particular, since the heat sink 26 to which the fan 25 is attached is fixed to the other surface of the Peltier element 6, the heat absorbed can be efficiently exchanged.

  The base portion 2a is provided with a thermistor 27 that measures the temperature of the crystal unit 3. The temperature control unit 7 is configured to perform feedback control of the Peltier element 6 while referring to the temperature measured by the thermistor 27, and can control the crystal resonator 3 to a desired constant temperature. Yes. However, the position of the thermistor 27 is not limited to the position on the base portion 2a, and may be freely designed as long as the temperature of the crystal resonator 3 can be measured.

The oscillation circuit 4 is a circuit for causing the crystal resonator 3 to oscillate, and includes a plurality of electric elements (not shown) and is incorporated in the oscillation substrate 5. The oscillation circuit 4 is electrically connected to the pair of electrodes 20 and 21 via lead electrodes formed on both surfaces of the crystal unit 3.
The oscillation substrate 5 is fixed by a metal plate 30 at a position provided outside the cell 2. More specifically, insulating heat conductive members 31 are disposed on both surfaces of the oscillation substrate 5. The oscillation substrate 5 is fixed in a state of being sandwiched from both sides by the metal plate 30 with the heat conductive members 31 interposed therebetween. That is, the oscillation substrate 5 is stably supported in a state in which the periphery is surrounded by the heat conductive member 31 and the metal plate 30.
The heat conductive member 31 is, for example, a silicone resin excellent in heat conductivity, a silicone resin using a silicone gel as a matrix, an acrylic resin, or a laminated resin including a copper layer. The metal plate 30 is, for example, an aluminum plate.

One surface of the Peltier element 8 is fixed to the lower surface of the metal plate 30 located below the oscillation substrate 5 by bonding or the like. A heat sink 33 to which a fan 32 is attached is fixed to the other surface of the Peltier element 8 (a surface opposite to the one surface).
The Peltier element 8 is connected to the temperature control unit 9, and one surface generates heat or absorbs heat by reversing the amount of current flowing from the temperature control unit 9 or polarity. In addition, the amount of heat generated and the amount of heat absorbed are also controlled. As a result, the Peltier element 8 can appropriately heat and cool the entire oscillation substrate 5 including the oscillation circuit 4 via the heat conductive member 31 and the metal plate 30.
In particular, since the heat sink 33 to which the fan 32 is attached is fixed to the other surface of the Peltier element 8, the heat absorbed can be efficiently exchanged.

The oscillation substrate 5 is provided with a thermistor 34 that measures the temperature of the oscillation circuit 4. The temperature control unit 9 performs feedback control of the Peltier element 8 while referring to the temperature measured by the thermistor 34, and can control the oscillation circuit 4 to a desired constant temperature. . However, the position of the thermistor 34 is not limited to the oscillation substrate 5 and may be freely designed as long as the temperature of the oscillation circuit 4 can be measured.
In addition, the pair of metal plates 30 fixing the oscillation substrate 5 is accommodated in the case 35 and is prevented from contacting the outside.

Next, the case where the viscosity of the sample liquid W is measured by the microsensing device 1 configured as described above will be described.
First, a reference solution (for example, a buffer solution such as water or physiological saline) is supplied through the supply tube 13 and the supply path 11 and introduced into the reaction tank 10 of the cell 2. At the same time, the oscillation circuit 4 applies a voltage between the detection electrode 20 and the counter electrode 21 to resonate the crystal unit 3. Then, the resonance resistance value at the resonance point, that is, the reference resistance value is measured in advance.

  Next, after the reference solution in the reaction tank 10 is discharged through the discharge tube 14 and the discharge path 12, the sample liquid W is supplied again through the supply tube 13 and the supply path 11 and introduced into the reaction tank 10. At the same time, the crystal unit 3 is resonated again. At this time, since the crystal unit 3 receives a resistance corresponding to the viscosity from the sample liquid W, the resonance resistance changes. And the measurement data which compared the resonance resistance value measured here and the reference | standard resistance value measured previously are acquired. Subsequently, the same measurement is performed for a plurality of different reference solutions, and measurement data for each reference solution is acquired. And based on the calibration curve of these several measurement data, the viscosity of the sample liquid W to measure can be measured.

  By the way, when performing the above-described measurement, the crystal unit 3 can be appropriately heated and cooled using the Peltier element 6 temperature-controlled by the temperature control unit 7, so that the temperature of the crystal unit 3 and the sample liquid in the reaction vessel 10 can be measured. It is possible to adjust the temperature of W to a constant temperature. Therefore, it is possible to suppress the resonance resistance value of the crystal resonator 3 from being changed due to the temperature change. Therefore, highly accurate measurement can be performed.

  Further, the oscillation circuit 4 can be appropriately heated and cooled using the Peltier element 8 temperature-controlled by the temperature control unit 9 in the same manner as the crystal resonator 3, so that the temperature of the oscillation circuit 4 can be adjusted to a constant temperature. it can. In addition, since the temperature can be controlled separately from the crystal unit 3, the temperature of the oscillation circuit 4 can be adjusted to a desired temperature without being influenced by the temperature of the crystal unit 3. Therefore, it is possible to suppress the electrical elements constituting the oscillation circuit 4 from becoming too high as in the conventional case. Therefore, measurement can be performed without causing problems such as failure, and a highly reliable apparatus can be obtained.

Further, unlike the conventional case where the temperature of a large metal block is controlled, it is only necessary to locally control the temperature of the crystal unit 3 and the oscillation circuit 4, so that the two Peltier elements 6 and 8 can be easily downsized. Can be planned. Therefore, it is easy to reduce the size of the two temperature control units 7 and 9 that control the temperature thereof. Therefore, the size of the entire apparatus can be reduced.
Further, since it is only necessary to control the temperature of the two miniaturized Peltier elements 6 and 8, power saving can be achieved as compared with the conventional case. Moreover, even if the calorific values of the crystal unit 3 and the oscillation circuit 4 are different from each other, the temperature can be controlled separately, so that the temperature can be controlled efficiently with an optimum temperature gradient suitable for each. Therefore, power saving can be achieved also in this respect.

Furthermore, since the crystal unit 3 and the oscillation circuit 4 can be controlled separately, for example, the crystal unit 3 is temperature-controlled with an error accuracy of ± 0.03 ° C., and conversely, the oscillation circuit 4 is ± It is also possible to make a difference in heating and cooling performance such as temperature control with a slightly low error accuracy of 0.1 ° C. Accordingly, it is possible to narrow down the temperature control region with high accuracy, and it is possible to suppress an increase in cost. Therefore, it can also lead to cost reduction.
In addition, since the temperature of the crystal unit 3 and the oscillation circuit 4 can be controlled separately, the temperature of the oscillation circuit 4 can be kept constant even when the temperature of the cell 2 is changed. The temperature characteristics can be accurately evaluated without being affected by the above.

As described above, according to the micro-sensing device 1 of the present embodiment, high-accuracy measurement can be performed using the crystal resonator 3 without causing defects of the electric elements constituting the oscillation circuit 4, Miniaturization, power saving, and cost reduction can be achieved.
Furthermore, in this embodiment, since the oscillation substrate 5 having the oscillation circuit 4 is surrounded by the heat conductive member 31 and the metal plate 30, the heat dissipation performance and the cooling performance are extremely excellent. Accordingly, the temperature of the oscillation circuit 4 can be quickly changed, and the temperature can be adjusted to a desired temperature efficiently in a short time, and further power saving can be easily achieved.
In particular, since the Peltier element 8 is fixed to the metal plate 30, heat can be transmitted through the metal plate 30 and the heat conductive member 31 without wasting heat. Also in this respect, the above-described effects can be made remarkable.

  In the above embodiment, the measurement object is the sample liquid W and the viscosity of the sample liquid W is measured as an example. However, the present invention is not limited to this case. For example, it is possible to analyze a characteristic of a specific substance (for example, an antibody or a protein) as a measurement target. This case will be briefly described.

  First, a predetermined amount of a fixed substance called a ligand or the like to which a specific substance (called an analyte or the like) binds through an adsorption reaction is fixed in advance on the surface of the crystal unit 3 including the detection electrode 20. Thereafter, a solution containing a specific substance is supplied through the supply tube 13 and the supply path 11 and introduced into the reaction tank 10 of the cell 2. At the same time, the oscillation circuit 4 applies a voltage between the detection electrode 20 and the counter electrode 21 to resonate the crystal unit 3.

Then, the specific substance is adsorbed and bound to the fixed substance, so that a minute mass change occurs near the surface of the crystal unit 3. Thereby, the resonance frequency of the crystal unit 3 changes. That is, a minute mass change can be measured as a resonance frequency change.
Subsequently, the above measurement is performed for each of solutions containing a plurality of specific substances. And the adsorption constant which adsorb | sucks to a fixed substance is computable from those measurement results.

In addition, when a buffer solution having a washing function or a buffer function (desorption function) is introduced into the reaction tank 10 after the above measurement is completed, the specific substance bonded to the fixed substance is desorbed. Also at this time, since a very small mass change occurs in the vicinity of the surface of the crystal unit 3, the resonance frequency of the crystal unit 3 changes. Therefore, as in the case described above, the desorption constant desorbed from the fixed substance can be calculated.
Thus, the adsorption / desorption constant of the specific substance with respect to the fixed substance can be obtained, and the characteristics of the specific substance can be analyzed.

In particular, this technique can be applied to various biochemical reactions such as DNA hybridization reactions, protein binding reactions, enzyme binding reactions, etc., and these reactions can be grasped easily and accurately. . Therefore, it can be applied to new drug development, biochemical fields, biotechnology fields, and the like.
According to the micro-sensing device 1 of the present embodiment, even when such an analysis is performed, the crystal resonator 3 and the oscillation circuit 4 can be temperature controlled separately, so that a highly accurate analysis can be performed.

Further, in the above-described embodiment, the temperature of the oscillation circuit 4 is specifically set to a temperature within the range of + 5 ° C. or more and less than + 30 ° C. above the room temperature so as to be an average operating temperature reached when operating at room temperature. The temperature control unit 9 may be set to control the temperature of the Peltier element 8.
The room temperature is a room temperature suitable for performing general experiments and measurements, and is an annual average room temperature (about 25 ° C.). Usually, when measuring and analyzing a measurement object, it can be considered that the measurement is performed at room temperature. When the oscillation circuit 4 is operated at such a room temperature, the temperature naturally reaches a temperature higher than the normal room temperature due to self-heating of the electric element, and the state becomes calm.

Therefore, by controlling the temperature of the oscillation circuit 4 so as to be within the above-described temperature range, it is possible to obtain a shape close to a natural state, and the oscillation circuit 4 is controlled to a constant temperature without performing excessive heating and cooling. be able to. Therefore, further power saving can be achieved.
If the temperature of the oscillation circuit 4 is higher than 30 ° C. above room temperature, the electrical elements constituting the oscillation circuit 4 are liable to malfunction, resulting in a decrease in life or the energy of the entire device. It becomes easy to invite increase in consumption.
The temperature is controlled so that the temperature of the oscillation circuit 4 is in the range of + 5 ° C. or more and less than + 30 ° C. from room temperature, but it is more preferable to control the temperature to be in the range of + 10 ° C. to + 15 ° C. .

In the case described above, the temperature of the oscillation circuit 4 is controlled so that the temperature is set in advance regardless of the use environment temperature at which measurement or analysis is actually performed. Thus, the temperature of the oscillation circuit 4 may be controlled to a constant temperature.
That is, after starting the apparatus, the temperature of the Peltier element 8 is controlled so as to follow the change in the use environment temperature so that the temperature of the oscillation circuit 4 becomes a predetermined value higher than the use environment temperature. After this, the Peltier element 8 may be set to be temperature controlled so as to maintain the temperature reached at the time of input.

  In this case, when the apparatus is started by turning on the power, the temperature control unit 9 controls the temperature of the Peltier element 8 so that the temperature of the oscillation circuit 4 is higher than the use environment temperature by a predetermined value. At this time, the temperature control unit 9 controls the temperature of the Peltier element 8 following the temperature change when the use environment temperature changes due to air conditioning or the like after activation. Therefore, the temperature of the oscillation circuit 4 is maintained at a temperature higher by a predetermined value than the use environment temperature. When the use environment temperature reaches an optimum temperature and measurement start is input, the temperature control unit 9 thereafter controls the temperature of the Peltier element 8 so as to maintain the temperature reached at the time of input. For example, when the predetermined value is 15 ° C., when the use environment temperature reaches 25 ° C. (optimum temperature) and measurement start is input, the temperature of the oscillation circuit 4 is maintained at 40 ° C. which has been reached at this time. Control the temperature as follows.

Usually, when the oscillation circuit 4 is operated, the temperature naturally reaches a temperature higher than the use environment temperature due to self-heating of the electric element, and is in a calm state. Therefore, by controlling the temperature of the oscillation circuit 4 so as to maintain a temperature higher than the operating environment temperature during measurement and analysis, it is possible to obtain a shape close to a natural state and oscillate without excessive heating and cooling. The circuit 4 can be controlled to a constant temperature. Therefore, it is easy to achieve further power saving.
In addition, since the temperature control is performed following the change in the use environment temperature so that the temperature of the oscillation circuit 4 becomes a predetermined value higher than the use environment temperature after the start-up, after inputting the measurement start, The measurement object can be immediately measured and analyzed without causing a time lag. Therefore, a device that is very easy to use and excellent in convenience can be obtained.

Further, in the above-described case, it is preferable to stop the temperature control when the use environment temperature has reached a temperature equal to or higher than a predetermined value at startup.
By setting in this way, the operating environment temperature reaches a high temperature (40 ° C. to 50 ° C.), for example, in a summer room, when the operating environment temperature has reached a predetermined value or more at startup. If so, the temperature control of the Peltier element 8 can be stopped.
Therefore, it is possible to prevent the temperature of the oscillation circuit 4 from being higher than a predetermined value by 40 ° C. to 50 ° C., and it is possible to prevent a problem from occurring due to this.

Furthermore, in the above case, it is more preferable to start the temperature control of the Peltier element 8 after the use environment temperature falls below the specified value.
By setting in this way, after the temperature control of the Peltier element 8 is stopped, the temperature control unit 9 starts the temperature control of the Peltier element 8 when the use environment temperature falls below a specified value due to air conditioning or the like. Thereby, the oscillation circuit 4 can be operated more safely, and the reliability can be improved.

  The technical scope of the present invention is not limited to the above embodiment, and various modifications can be made without departing from the spirit of the present invention.

  For example, in the above-described embodiment, the crystal resonator and the oscillation circuit are heated and cooled using the Peltier element, but the present invention is not limited to the Peltier element. If at least the crystal resonator and the oscillation circuit can be heated and cooled, respectively, the heating and cooling unit can be employed.

Moreover, although the flow type cell was mentioned as an example in the said embodiment, it may not be a flow type if it is a cell provided with the reaction tank.
For example, as shown in FIG. 2, a well-type cell 40 may be used in which the upper part of the reaction tank 10 is opened and a measurement object is introduced into the reaction tank 10 by dropping or the like from above. Even in this case, the same effect can be obtained.
However, when a flow-type cell is used, the measurement object can be quickly introduced into the reaction tank 10 or the measurement object can be quickly discharged from the reaction tank 10, which is efficient. Since measurement and analysis can be performed, it is more preferable.

  In the above-described embodiment, the case where only the detection electrode 20 that is one of the electrodes is configured to come into contact with the measurement object has been described as an example. However, for example, the measurement object is an insulating substance such as a gas. In this case, both electrodes (detection electrode 20 and counter electrode 21) may be configured to contact the measurement object. What is necessary is just to change this point suitably according to a measurement object.

W ... Sample liquid (object to be measured)
DESCRIPTION OF SYMBOLS 1 ... Micro sensing apparatus 2 ... Cell 3 ... Crystal oscillator 4 ... Oscillation circuit 5 ... Oscillation board 6 ... Peltier device (1st heating-cooling part)
7 ... Temperature controller (first temperature controller)
8 ... Peltier element (second heating / cooling section)
9 ... Temperature controller (second temperature controller)
10 ... Reaction tank 20, 21 ... Electrode

Claims (7)

A cell having a reaction vessel into which an object to be measured is introduced;
A pair of electrodes to which a voltage is applied on both sides is formed, and at least one electrode is disposed in the cell so as to be in contact with the measurement object introduced into the reaction vessel,
An oscillation substrate disposed outside the cell and having an oscillation circuit for resonating the crystal resonator;
A first heating / cooling unit that heats and cools the cell simultaneously with the crystal unit;
A second heating / cooling section for heating and cooling the oscillation circuit;
A first temperature control unit for controlling the temperature of the first heating / cooling unit;
A second temperature control unit for controlling the temperature of the second heating / cooling unit to control the temperature of the oscillation circuit separately from the crystal unit,
The micro-sensing device according to claim 1, wherein the first heating / cooling unit includes a first Peltier element having one surface fixed to a lower surface of a base portion of the cell. The microsensing device according to claim 1,
The other surface of the first Peltier element is fixed to a heat sink to which a fan is attached . A cell having a reaction vessel into which an object to be measured is introduced;
A pair of electrodes to which a voltage is applied is formed on both surfaces, and a crystal resonator disposed in the cell so that at least one electrode is in contact with the measurement object introduced into the reaction vessel;
An oscillation substrate disposed outside the cell and having an oscillation circuit for resonating the crystal resonator;
A first heating / cooling unit for heating and cooling the crystal unit;
A second heating / cooling section for heating and cooling the oscillation circuit;
A first temperature control unit for controlling the temperature of the first heating / cooling unit;
A second temperature control unit for controlling the temperature of the second heating / cooling unit in order to control the temperature of the oscillation circuit separately from the crystal unit;
Consists of
The first heating / cooling unit is a first Peltier element having one surface fixed to the lower surface of the base portion of the cell,
Insulating heat conductive members disposed on both sides of the oscillation substrate;
Comprising a metal plate that sandwiches and fixes the oscillation substrate from both sides via the thermally conductive member,
The micro-sensing device, wherein the second heating / cooling unit is a second Peltier element fixed to the metal plate . In the microsensing device according to claim 3 ,
A microsensing device having a case for housing the metal plate . In the microsensing device according to any one of claims 1 to 4 ,
In order to control the temperature error of the crystal resonator more accurately than the temperature error accuracy of the oscillation circuit, the temperature control accuracy of the first temperature control unit is higher than the temperature control accuracy of the second temperature control unit. A micro-sensing device characterized by: In the microsensing device according to any one of claims 1 to 5 ,
The second temperature control unit controls the temperature of the second heating / cooling unit so that the temperature of the oscillation circuit is within a range of + 5 ° C. or more and less than + 30 ° C. than room temperature. Micro sensing device. In the microsensing device according to any one of claims 1 to 4 ,
The second temperature control unit follows the change in the use environment temperature so that the temperature of the oscillation circuit is higher than the use environment temperature by a predetermined value after startup. A micro-sensing device characterized by controlling the temperature of the second heating / cooling unit so that the temperature reached at the time of input is maintained after the start of measurement is input .

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