JP2002148295A - Method and instrument for frequency measurement and analytical equipment - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a technology which can shorten the time needed for measurement for an instrument and a method for frequency measurement, which measure the oscillation frequencies of crystal oscillators in a liquid. SOLUTION: Using this frequency measuring method, the crystal oscillators 61 to 64 are oscillated intermittently but are not oscillated continuously. Consequently, the crystal oscillators are oscillated with a small vibration energy, and the time needed before the oscillation frequencies of the crystal oscillators 61 to 64 become stable in liquid become shorter than that, when the crystal oscillators are continuously oscillated. Further, two or more of the crystal oscillators 61 to 64 are not made to oscillate at the same time, so two or more of the crystal oscillators will not oscillate at the same time, to interfere with each other and measurements can be take without lowering the stability of the oscillation frequencies due to interference.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a frequency measuring method, a frequency measuring device and an analyzing device, and more particularly to a method and an analyzing device for analyzing a reaction state, and more particularly to a frequency measuring device for measuring an oscillation frequency of a crystal oscillator in a liquid. Also, the present invention relates to a frequency measuring method and an analyzer that detects a change in an oscillation frequency measured by such a frequency measuring device and analyzes components in a liquid and analyzes a reaction rate.

[0002]

2. Description of the Related Art In recent years, when a crystal oscillator having a specific substance disposed on the surface of an electrode is oscillated in a liquid such as blood, components in the liquid are bonded to the surface of the crystal oscillator, and An analyzer that analyzes the reaction rate of a specific component in a sample or the like by using the phenomenon that the oscillation frequency of a crystal oscillator decreases in accordance with the mass of the crystal oscillator has been proposed.

The configuration of the analyzer is shown by reference numeral 101 in FIG. The analyzer 101 includes a computer 102,
It has a frequency counter 103, an oscillator 104, a DC power supply 105, and a crystal oscillator 106.

[0004] The crystal oscillator 106 has a disk made of quartz and electrodes disposed on the front and back sides thereof, and is configured to be able to oscillate even when immersed in a liquid. On the surface of one of the electrodes, a predetermined reaction material configured to react with a specific component and adsorb the component is arranged, and the reaction material is immersed in the crystal oscillator 106 in a liquid. Exposure to liquids.

In order to analyze a reaction state between a specific component in a sample such as blood and a reaction material by the analyzer 101 having the above-described configuration, first, the crystal oscillator 106 is placed in the atmosphere. , The DC power supply 105 is activated to apply a DC voltage to the oscillator 104. Then, the crystal oscillator 106 connected to the oscillator 104 oscillates at a predetermined oscillation frequency.

The change in the oscillation frequency of the crystal oscillator 106 is shown by a curve (X) in FIG. The horizontal axis of the graph in FIG. 7 indicates time, and the vertical axis indicates the oscillation frequency of the crystal oscillator 106. The symbol _Fo indicates the oscillation frequency of the crystal oscillator 106 in the atmosphere.

A quartz oscillator 106 oscillating at an oscillation frequency F _o in the atmosphere is mixed with a solution 1 placed in a water tank 107.
08. Here, the solution 108 generally uses a saline solution or the like, and is called a buffer solution. In FIG. 7, the time when the crystal oscillator 106 is immersed in the solution 108 is represented by _a symbol t _a
Is shown in When the crystal oscillator 106 is immersed in the solution 108, the load applied to the crystal oscillator 106 becomes larger than that in the atmosphere, so that the oscillation frequency of the crystal oscillator 106 is greatly reduced as shown by a curve (X). , Greatly attenuated,
Eventually, it becomes stable at a predetermined frequency. FIG. 7 shows the predetermined frequency in the code F _s. The oscillation frequency of the crystal oscillator 106 is constantly detected by the frequency counter 103, and the detection result is output to the computer 102 as needed. When the fluctuation of the oscillation frequency is within the predetermined range for a predetermined time or more, the computer 102 determines that the oscillation frequency has stabilized, and notifies the user to that effect. In Figure 7, by the symbol F _s, indicating that the oscillation frequency of the crystal oscillator 106 is stabilized.

[0008] The user, after the oscillation frequency has been notified that stabilized at F _s, injecting the sample to be analyzed in the water tank 107. In FIG. 7, time t _b indicates the time at which the sample was injected. When the sample is injected into the water tank 107, the sample is diffused in water to generate a solution having a predetermined concentration, and a specific component in the solution reacts with a reaction material disposed on one electrode surface of the crystal oscillator 106. , Adsorb on the surface of the reaction material. Then, the oscillation frequency of the crystal oscillator 106 decreases according to the mass of the adsorbed component.

[0009] As described above, the computer 102 is provided with the crystal oscillator 10 input from the frequency counter 103 as needed.
From the oscillation frequency of No. 6, the reaction state of the specific component adsorbed on the surface of the reaction material can be analyzed. As an example of the analysis, in order to determine the reaction rate of a particular component of the reaction material and the sample, after sample loading in FIG. 7, the crystal oscillation at a given time Δt between the predetermined time t _c and a predetermined time t _d Child 10
The change amount ΔF of the oscillation frequency of No. 6 is obtained. Crystal oscillator 10
6 and the mass Δm of the component adsorbed on the surface of the reaction material 115 during the predetermined time Δt, C
Is a predetermined constant, it is known that a relational expression of ΔF = −C × Δm (1) is established. From the above expression (1), it is known that a specific expression adsorbed on the surface of the reaction material in a predetermined time is obtained. Since the mass change Δm of the component is determined, the reaction rate between the reactant and the specific component can be determined.

[0010] However, the analyzer 1 having the above-described configuration is used.
At 01, an AC signal is always supplied to the crystal oscillator 106 to continuously oscillate the crystal oscillator 106. Underwater, the load applied to the crystal oscillator 106 increases,
In order to continuously oscillate this, it is necessary to give a large vibration energy. However, if such a large vibration energy is given, the oscillation frequency of the crystal oscillator 106 is reduced to a frequency stable in the liquid, for example, from 2 to 2. There has been a problem that a considerably long time of three hours is required.

In the above-described configuration, one crystal oscillator 106 can measure only the reaction speed when one type of specific component reacts with one type of reaction material. In order to analyze the reaction state of the component (1), it is necessary to prepare a plurality of crystal oscillators and reaction materials and detect the oscillation frequency of each crystal oscillator. However,
When a plurality of crystal oscillators 106 oscillate at the same time, the respective crystal oscillators 106 interfere with each other via a circuit or the like connected to the crystal oscillators 106, and the oscillation frequency becomes unstable. Had the problem of doing so.

[0012]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned disadvantages of the prior art, and its object is to greatly reduce the time required for analyzing the reaction state of components using a crystal oscillator. To provide a technique that enables highly accurate analysis by stably oscillating the crystal oscillators without interfering with each other even when multiple types of crystal oscillators are used. It is in.

[0013]

According to a first aspect of the present invention, there is provided a method for measuring an oscillation frequency of an oscillator in a liquid while the oscillator is immersed in the liquid. A measuring method, wherein the oscillator is intermittently oscillated, and an oscillation frequency of the oscillator is measured. The invention according to claim 2 is the frequency measurement method according to claim 1, wherein the oscillation frequency of the oscillator in a liquid is measured using the plurality of oscillators, wherein the plurality of oscillators are intermittently arranged one by one. Oscillation is performed, and the oscillation frequency of each oscillator is individually measured. According to a third aspect of the present invention, in the frequency measuring method according to the second aspect, the same liquid or different liquids are respectively arranged in different containers, and the oscillations are respectively applied to the respective liquids arranged in the respective containers. It is characterized by immersing the children one by one. According to a fourth aspect of the present invention, there is provided an oscillation unit including a plurality of oscillators configured to be able to oscillate in a liquid, an oscillation control circuit for oscillating each of the oscillators, and individually adjusting an oscillation frequency of each of the oscillators. A frequency measuring device including a measuring circuit for measuring, wherein the oscillating unit is configured to intermittently oscillate each of the oscillators one by one. According to a fifth aspect of the present invention, in the frequency measuring device according to the fourth aspect, the oscillating unit has a switch circuit for switching a connection state between the oscillator and the oscillation control circuit. According to a sixth aspect of the present invention, there is provided an analyzer, comprising the frequency measuring device according to any one of the fourth and fifth aspects,
Analyzing means for obtaining the amount of the component in the liquid adhering to the oscillator based on the oscillation frequency of the oscillator in the liquid measured by the frequency measuring device.

According to the frequency measuring method of the present invention, since the oscillator is oscillated intermittently, the oscillator does not oscillate continuously. For this reason, the oscillator can be operated with small vibration energy as compared with the case where the oscillator is continuously oscillated, so that the time required for the oscillation frequency to stabilize in the liquid is shorter than before. .

In the frequency measuring method of the present invention,
When measuring the oscillation frequency of each oscillator using a plurality of oscillators, each oscillator is oscillated one by one. For this reason, two or more oscillators operate at the same time, and there is no interference between the oscillators, so that the conventional problem that the stability of the oscillation frequency of each oscillator decreases due to such interference does not occur. .

Further, the frequency measuring apparatus of the present invention has an oscillating unit provided with an oscillator capable of oscillating in a liquid, and the oscillating unit intermittently oscillates the oscillator. In particular, the time required for the oscillation frequency of the oscillator to stabilize in liquid is shortened.

Further, in the frequency measuring apparatus of the present invention,
The oscillating unit includes, for example, a switch circuit, and intermittently oscillates a plurality of oscillators one by one. Therefore, two or more oscillators do not oscillate at the same time and interfere with each other, so that the measurement accuracy of the oscillation frequency does not decrease.

Further, the analyzer of the present invention comprises an analyzing means for determining the amount of the component in the liquid adhering to the oscillator based on the oscillation frequency of the oscillator, and the frequency measuring device of the present invention. . As described above, since the oscillation frequency of the oscillator is measured by the frequency measuring device of the present invention, the oscillation frequency of the oscillator in the liquid is stabilized in a short time, and the time required for analysis can be significantly reduced as compared with the conventional case.

[0019]

An embodiment of the present invention will be described below with reference to the drawings. Reference numeral 1 in FIG. 1 indicates a reaction state analyzer according to one embodiment of the present invention. The analyzer 1 includes an oscillator 4, an oscillator 30, a frequency counter 3, and a computer 2. The frequency counter 3 has a function of sending a signal to the switch 20 and controlling it.

The oscillator 4 is an example of the oscillation control circuit of the present invention, and operates when the power supply 5 is started, and is configured to output an AC signal of a predetermined frequency to the switch 20. Oscillation unit 30 includes a plurality of crystal oscillator ₆₁ through _4, a switching device 20. Here, four crystal oscillators 6
It assumed to have _{1-6 4.}

As shown in FIGS. 3A and 3B, the quartz oscillators 6 _{1 to} 6 ₄ have a disk 14 made of quartz and a surface side of the disk 14, respectively. And electrodes 12 and 13 made of gold, which are arranged on the rear side and the rear side, respectively. Electrode 13 on the back surface side is sealed with a resin 16 shown in FIG. 3 (b), even in a state where the crystal oscillator ₆₁ through ₄ were placed in a liquid, the electrode 3 on the back side is exposed to water Instead, it is configured to be able to oscillate. On the other hand, a reaction material 15 configured to react with a specific component and adsorb the component is disposed on the surface of the electrode 12 on the front surface side. This reaction material 15
It is adapted to be exposed to water in a state that put the crystal oscillator 6 _{1-6 4} in the water. In addition, four of the crystal oscillator 6 ₁ -
Each electrode 12 surface 6 ₄ on the surface side, are arranged different reaction material 15, respectively.

FIG. 2 shows an equivalent circuit diagram of FIG. Switch 2
0 is an example of the switch circuit of the present invention, and has the same number of switches 21 _{1 to} 21 ₄ as the crystal oscillators 6 _{1 to} 6 ₄ . Each of the switches 21 _{1 to} 21 ₄ is turned on or off in accordance with a control signal supplied from a frequency counter 3 described later.
When conducting, the oscillator 4 and each of the switches 21 ₁ to 21 ₁
And it is configured to be able to oscillate the 21 ₄ to crystal oscillator ₆₁ through ₄ connected respectively.

The frequency counter 3 is an example of a measurement circuit of the present invention, by measuring the oscillation frequency of the crystal oscillator ₆₁ through ₄ are configured to be able to output to the computer 2. Also sends a signal to the switching device 20 has a function for switching the switch 21 ₁ to 21 _4.

The computer 2 is an example of the analysis means of the present invention. The computer 2 detects a reaction rate of a component in a liquid on the basis of the measured oscillation frequency so that the component can be analyzed. It is configured.

[0025] In the analyzer 1 of the above configuration, for example, a specific component in a sample such as blood, to analyze the reaction state between the reaction material 15 respectively disposed on the surface of the crystal oscillator ₆₁ through ₄ , first, in a state where the crystal oscillator ₆₁ through ₄ is placed in the atmosphere or in solution, to operate the oscillator 4 by starting the DC power source 5. Then, the oscillator 4 outputs an AC signal to the switch 20.

The AC signal output to the switching device 20 is supplied to the four switches 21 ₁ to 21 ₄ in the switching device 20.
Each of the switches 21 _{1 to} 21 ₄ is turned on or off according to a control signal output from the frequency counter 3. 5 shows a timing chart of the conducting state of the switch 21 ₁ to 21 ₄ in the switching device 20. As shown in FIG. 5, four switches 21 ₁ to 21 ₄ in the switching device 20 is both a predetermined time (here, for example, less than 1 second) Delta] t only conductive, and successively conducting one by one. For this reason, two or more switches do not conduct at the same time. Here, the predetermined time Δt is set to 100 msec.

Four switches 21₁~ 21_FourOf which
When one of the switches is turned on for a predetermined time Δt, the switch that has turned on is turned on.
Switch 21₁~ 21_FourAny one crystal oscillator connected to
Child 6 ₁~ 6_FourIs supplied with an AC signal for a predetermined time Δt.
Crystal oscillator 6₁~ 6_FourOscillates. Each switch 21₁~
21_FourAre sequentially conducted one by one, so that each crystal oscillator 6₁~
6_FourOscillate one by one for a predetermined time Δt. Each water
Crystal oscillator 6₁~ 6_FourThe oscillation frequency of
Therefore, it is detected. The detected oscillation frequency is
Output to the computer 2.

[0028] shown by the curve (A) in FIG. 4 the change in the oscillation frequency of each quartz oscillator ₆₁ through _4. The horizontal axis of the graph in FIG. 4 represents time and the vertical axis represents the oscillation frequency of the crystal oscillator ₆₁ through _4. Each crystal oscillator ₆₁ through ₄ as shown by the curve (A),
Oscillation for a predetermined time Δt is repeated at predetermined intervals. Since no oscillation occurs during the period other than the predetermined time Δt and the oscillation frequency becomes 0, the curve (A) showing the measurement result of the oscillation frequency
Becomes a pulse-like curve as shown in FIG.

The code F _o in Figure 4 shows the oscillation frequency of the crystal oscillator ₆₁ through ₄ in the atmosphere. In the atmosphere, the oscillation frequency F _o four of which oscillates in the crystal oscillator 6 _{1-6 4}
And placed in four cell 7 _{1-7 4} respectively different.
Each cell 7 has respective solution 8 is put in the _{1-7 4,} each crystal oscillator ₆₁ through ₄ are immersed in the solution 8 respectively. FIG. 4 shows the time obtained by immersing the crystal oscillator ₆₁ through ₄ the sign t _a.

When each of the crystal oscillators 6 _{1 to} 6 ₄ is immersed in the solution 8, the load applied to the crystal oscillators 6 _{1 to} 6 ₄ becomes larger than that in the atmosphere. Child 6 ₁
The oscillation frequency F of the 6 ₄ is greatly reduced.

Thereafter, the oscillation frequency F of the crystal oscillators 6 _{1 to} 6 ₄ largely decreases as shown by the curve (A), then attenuates, and eventually stabilizes at the predetermined frequency. Computer 2
Analyzes the change state of the oscillation frequency output from the frequency counter 3.

As shown in FIG. 4, since the crystal oscillator ₆₁ through ₄ of the present embodiment is intermittently repeated to oscillate a predetermined time Delta] t, the vibration energy of the crystal oscillator ₆₁ through ₄ Is smaller than the vibration energy of a conventional crystal oscillator that has been continuously oscillated by supplying an AC signal constantly.
Therefore, the amount of attenuation is smaller and the time required for the oscillation frequency to be stable is shorter than that of a conventional crystal oscillator that vibrates with large vibration energy. Conventionally, it took 2 to 3 hours or more for the oscillation frequency of the crystal oscillator to stabilize.
Time to _{1-6 4} oscillation frequency is stabilized becomes about 30 minutes, it was possible to greatly shorten the time.

The computer 2 determines that the oscillation frequency has stabilized at the predetermined frequency if the time during which the fluctuation of the oscillation frequency falls within the predetermined range continues for a predetermined time or more, and notifies the user of this. In Figure 4, it shows a stable oscillation frequency code F _s.

[0034] Thus after the oscillation frequency of the crystal oscillator ₆₁ through ₄ was stabilized at F _s, the user, in the solution 8 which is placed in each cell 7 _{1-7 4,} samples are each analyzed throw into. Code t _e in FIG. 4 indicates the time the sample is introduced. When turning on the sample in the solution 8, the sample solution dissolved in water are generated, a particular component of the generated solution was placed on one electrode surface of the quartz oscillator ₆₁ through ₄ reaction material 15 react with each other, and a specific component starts to be adsorbed on the surface of the reaction material 15. Then, the oscillation frequencies of the crystal oscillator ₆₁ through ₄ in accordance with the mass of the adsorbed component decreases.

The computer 2, than the oscillation frequency of the crystal oscillator ₆₁ through ₄ input at any time from the frequency counter 3, as described above, to analyze the reaction conditions of the components adsorbed on the reaction member 15 surface. For example, the change ΔF of the oscillation frequency of the crystal oscillators 6 _{1 to} 6 _{4 at} the predetermined time Δt is obtained, and the mass change Δm of the component adsorbed on the surface of the reaction material 15 at the predetermined time is obtained based on the above equation (1). The reaction material 15
And the reaction rate of the component adsorbed thereon.

As described above, the analyzer 1 of the present embodiment
Has _four crystal oscillators 6 _{1 to} 6 ₄ , and each crystal oscillator 6
On the surface of the _{1-6 fourth} electrode 12, since different reaction material 15 is disposed, respectively, by detecting four crystal oscillator ₆₁ through ₄ separate the change in the oscillation frequency, respectively, four It reacts with the different types of reactants 15, respectively, and can simultaneously analyze the reaction states of the four types of components contained in the same sample.

Since each of the crystal oscillators 6 _{1 to} 6 ₄ is sequentially and intermittently turned on by the switch 20 for a predetermined time Δt as described above, two or more crystal oscillators 6 _{1 to} 6 ₄ are simultaneously operated. The crystal oscillator does not oscillate. For this reason,
Since two or more crystal oscillators oscillate at the same time and the oscillations of the crystal oscillators do not interfere with each other, highly accurate analysis is possible.

[0038] In the present embodiment, is provided with the four crystal oscillator ₆₁ through _4, the number of the crystal oscillator of the present invention is not limited thereto, four or more, for example ten The number may be four or less, for example, two.

In this embodiment, each crystal oscillator 6 ₁
6 ₄ to oscillate in the air, it oscillated each crystal oscillator 6 ₁ -
6 ₄ While immersed in the solution 8, the present invention is not limited to this, the crystal oscillator ₆₁ through ₄ in the air
Oscillation may be started in a state of being immersed in the solution 8 without causing oscillation.

Further, the analyzer 1 of the present invention has one oscillator 4 and the oscillating unit 30 has the switch 20, but the present invention is not limited to this, and the crystal oscillators 6 _{1 to} 6 are not limited to this. _Four
With the number only oscillator 4, and the oscillation portion 30 is provided with the same number of switches and the crystal oscillator ₆₁ through ₄ and the oscillator 4, which switches between the oscillator 4 and crystal oscillator ₆₁ through ₄ are inserted one by one between each may be configured so as to connect the respective oscillators 4 and the crystal oscillator ₆₁ through ₄ when conducting.

In this case, the predetermined time Δt during which the crystal oscillators 6 _{1 to} 6 ₄ oscillate is set to 100 msec. However, the predetermined time Δt in the present invention is not limited to this, and is, for example, 1 msec to 10 sec. It may be a range.

Further, a solution 8 which is placed in four of the cells 7 _{1-7 4,} although analyzed contain the same samples, the present invention is not limited thereto, for example, all of the cells 7 ₁ ~ 7 ₄
Alternatively, different samples may be put in the analyzer and each sample may be analyzed.

Although the control function of the switch 20 is given to the frequency counter 3 here, the present invention is not limited to this. For example, the switching may be performed using the computer 2.

[0044]

The time required for frequency measurement can be reduced.

[Brief description of the drawings]

FIG. 1 is a diagram illustrating an analyzer according to an embodiment of the present invention.

FIG. 2 is an equivalent circuit diagram illustrating an analyzer according to one embodiment of the present invention.

FIG. 3A is a plan view illustrating a configuration of a crystal oscillator used in the analyzer of the embodiment. FIG. 3B is a cross-sectional view illustrating a configuration of a crystal oscillator used in the analyzer of the embodiment.

FIG. 4 is a graph illustrating a change over time of the oscillation frequency of the crystal oscillator used in the analyzer according to the embodiment.

FIG. 5 is a timing chart for explaining the operation of a switch used in the analyzer of the present embodiment.

FIG. 6 is a diagram illustrating a configuration of a conventional analyzer.

FIG. 7 is a graph illustrating a change over time of an oscillation frequency of a crystal oscillator used in a conventional analyzer.

[Explanation of symbols]

2. Computer (analyzing means) 3. Frequency counter (measuring circuit) 4. Oscillator (oscillation control circuit)
6 _{1-6 4} ...... crystal oscillator (oscillator) 20 ...... switcher
(Switch circuit) 30 Oscillator

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Ken Maehira 2500 Hagizono, Chigasaki City, Kanagawa Prefecture, Japan Vacuum Engineering Co., Ltd. (72) Inventor Furu Ko 2500 Hagizono, Chigasaki City, Kanagawa Prefecture, Japan Vacuum Engineering Co., Ltd. (72 Inventor Junpei Yuyama 2500 Hagizono, Chigasaki-shi, Kanagawa F-term in Japan Vacuum Engineering Co., Ltd. (reference) 2G029 AA02 AB06 AD01 AH00

Claims (6)

[Claims] 1. A frequency measuring method for measuring an oscillation frequency of an oscillator in a liquid while the oscillator is immersed in a liquid, wherein the oscillator is oscillated intermittently. A frequency measuring method characterized by measuring an oscillation frequency. 2. The frequency measuring method according to claim 1, wherein an oscillation frequency of the oscillator in a liquid is measured using the plurality of oscillators, wherein the plurality of oscillators are intermittently oscillated one by one. And measuring the oscillation frequency of each oscillator individually. 3. The liquid crystal device according to claim 2, wherein the same liquid or different liquids are arranged in different containers, and the oscillators are immersed one by one in the liquids arranged in the containers. Frequency measurement method. 4. An oscillation section having a plurality of oscillators configured to be able to oscillate in a liquid, an oscillation control circuit for oscillating each of the oscillators, and a measurement for individually measuring an oscillation frequency of each of the oscillators. A frequency measuring device comprising: a circuit; and wherein the oscillating unit is configured to intermittently oscillate each of the oscillators one by one. 5. The frequency measuring device according to claim 4, wherein said oscillating unit has a switch circuit for switching a connection state between said oscillator and said oscillation control circuit. 6. The oscillator according to claim 4, wherein said oscillator is based on an oscillation frequency of said oscillator in a liquid measured by said frequency measuring device. An analyzer for determining the amount of the component in the liquid adhering to the liquid.