JP2006029874A - Sensor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sensor capable of detecting highly sensitively an environmental pollutant, dioxin, for example, existing in a micro amount, or a marker protein or the like, in a short time. <P>SOLUTION: A frequency difference between, for example, 9MHz of frequency signal from an oscillation circuit for oscillating a quartz oscillator and, for example, 10MHz of reference frequency signal is taken out using the quartz oscillator formed on a surface with an adsorption layer for adsorbing a sensing substance, the 1MHz of frequency signal, that is the frequency difference, is multiplied ten times, for example, to be counted by a counter, and a concentration or the presence of the sensing substance is detected based on the counted value. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention uses a sensor vibrator, such as a quartz crystal vibrator, in which an adsorption layer for adsorbing a sensing object is formed on the surface thereof, and the natural frequency changes due to the adsorption of the sensing object. The present invention relates to a sensing device that senses a sensing object by detecting a change in frequency.

In the field of biotechnology or environmental conservation, it is often necessary to detect the presence or concentration of trace amounts of substances, and therefore, establishment of measurement techniques for trace amounts of pollutants or organic substances is desired. Examples of the sensing target include infectious disease bacteria, dioxins, PCBs, marker proteins, stress markers, and the like. Among the pollutants, there is dioxin that has recently attracted attention. As a method for measuring this dioxin, a method defined in the official method (JIS) using a high-resolution gas chromatograph mass spectrometer is known. An ELISA method (enzyme-immobilized immunoassay) is known as a simple method. According to the gas chromatograph mass spectrometer, it is possible to carry out high-accuracy trace analysis on the order of 10 ⁻¹² g / ml, but the price of the apparatus is extremely high, and therefore the analysis cost is considerably high. There is a disadvantage that the analysis requires a long period of time. In addition, the ELISA method is lower in apparatus price and analysis price than the gas chromatograph mass spectrometer and has a short analysis time, but has a problem that the analysis accuracy is as low as 10 ⁻⁹ g / ml.

  Therefore, the present inventor focuses on the crystal resonator as a measuring device for contaminants such as dioxin because the natural frequency changes according to the amount of the object to be detected attached to the crystal resonator. On the other hand, there is a technique described in Patent Document 1 as a chemical sensing device that identifies an adsorbed gas using a crystal resonator. This device includes a sampling circuit that outputs an absolute value of a difference frequency between an oscillation frequency of a sensor vibrator and a reference frequency generated by a reference vibrator, and a frequency dividing circuit that divides the difference frequency by a predetermined frequency dividing ratio. , And the frequency of the divided output is counted by a counter with a clock pulse, and the oscillation frequency of the sensor vibrator is obtained by an arithmetic unit based on the counted period. According to this chemical sensing device, since the difference frequency is obtained, the absolute value of the frequency to be measured can be reduced, and there is an advantage that measurement with high resolution is possible without expanding the measurement range.

  By the way, when a change in the difference frequency is regarded as a change in the period of the frequency signal, for example, in order to obtain a resolution of 1 Hz when the difference frequency is 50 kHz, there is a clock of 2.5 GHz or more as the clock for counting the period. Necessary. For this reason, it is not easy for the technique of Patent Document 1 to generate such a high-frequency clock, so that the difference frequency is divided by, for example, 1/256.

  However, since the above-mentioned apparatus has a multi-stage frequency dividing circuit, phase noise increases, and it is difficult to ensure high measurement accuracy. For example, assuming that a minute frequency change of 0.01 Hz is captured using a 9 MHz crystal resonator, the number of stages of the frequency dividing circuit must be increased to, for example, 1024 stages, but the phase noise is considerably large. Become. As a result, the application range is limited, and it is difficult to apply when it is required to detect a very small amount of a substance such as dioxin with high sensitivity.

  On the other hand, if the pulse number itself is counted instead of counting the pulse frequency of the difference frequency, the counter side cannot capture the change in the difference frequency unless the pulse to be counted changes by one pulse. In order to capture the change with the counter, since measurement must be continued until it appears as a change of one pulse, a measurement time as long as 100 seconds is required.

Paragraph 0014 of JP-A-6-241972

  The present invention has been made under such circumstances, and it is an object of the present invention to provide a sensing device capable of sensing a minute amount of, for example, environmental pollutants and organic substances with high sensitivity and in a short time.

The sensing device of the present invention uses a sensor vibrator in which an adsorption layer for adsorbing a sensing object is formed on the surface thereof, and the natural frequency changes due to the adsorption of the sensing object. In a sensing device that senses a sensing object by changing the number,
An oscillation circuit for oscillating the sensor vibrator;
A reference frequency generator for generating a reference frequency signal;
A frequency difference output means for extracting a frequency difference between the frequency signal from the oscillation circuit and the reference frequency signal and outputting a frequency signal of the frequency difference;
Multiplication means for multiplying the frequency signal of the frequency difference;
And a counting means for counting the frequency signal multiplied by the multiplication circuit.

  As a more specific example of the present invention, a low-pass filter that passes the frequency signal of the frequency difference is provided after the frequency difference output unit, and the multiplication unit amplifies the frequency signal that has passed through the low-pass filter and the frequency. An example may be given in which the amplifier is configured to output a signal including a harmonic corresponding to a frequency signal obtained by multiplying the signal. Moreover, the structure which provided the filter which allows the frequency signal multiplied by the said multiplication means to pass after the multiplication means can be mentioned.

  In the present invention, a frequency difference between an oscillation circuit that oscillates a sensor resonator such as a crystal resonator and a reference frequency signal is extracted, and the frequency signal of the frequency difference is multiplied and counted. Even if the frequency change is small, the frequency change is multiplied, so that the small change can be captured in a short time. For example, it takes 100 seconds to capture a frequency change of 0.01 Hz with a counter, but if the frequency change is 10 times, it can be captured in 10 seconds. Therefore, the sensing substance can be sensed with high sensitivity and in a short time.

  FIG. 1 is a diagram showing an overall configuration of an embodiment of a sensing device according to the present invention. Reference numeral 1 denotes a sensor unit. The sensor unit 1 is a transducer for a sensor. For example, one surface of a crystal unit 11 having an AT-cut fundamental wave frequency of 9 MHz (about 9 MHz) is sealed with quartz or the like, and the other side. These surfaces are exposed, and are configured as, for example, a Langevin type vibrator immersed in the solution 12 in the container 10 in which the substance to be detected exists. The surface in contact with the solution in the crystal unit 11 includes an adsorption layer made of, for example, an antibody or a receptor molecule for selectively adsorbing (capturing) a sensing target substance, for example, an adsorption containing an antibody for adsorbing dioxin. A layer is formed. An oscillation circuit 13 oscillates the crystal unit 11.

Reference numeral 2 denotes a reference frequency generation unit that outputs a reference frequency signal of 10 MHz of, for example, about 1 × 10 ⁻⁹ / day, which has extremely high frequency stability. Reference numeral 3 denotes a heterodyne detector corresponding to frequency difference output means for extracting the frequency difference between the frequency signal from the oscillation circuit 13 and the reference frequency signal from the reference frequency generator 2 and outputting the frequency signal of the frequency difference. A low-pass filter (analog filter) 4 including capacitive elements 41 and 42 and an inductor 43 is connected to the subsequent stage of the heterodyne detector 3. This low-pass filter 4 is for removing noise contained in the frequency signal from the heterodyne detector 3 and allowing the frequency signal of the frequency difference, that is, the frequency signal of 1 MHz to pass through.

  An amplifier 5 that is an amplifying unit is connected to the subsequent stage of the low-pass filter 4, and this amplifier 5 has a function of amplifying the level of the frequency signal from the low-pass filter 4, but generates a harmonic during this amplification. . This harmonic includes a harmonic corresponding to a frequency multiplied by 10 of the frequency signal of 1 MHz, and therefore, in this example, the amplifier 5 corresponds to a multiplication means. Therefore, the frequency signal output from the amplifier 5 includes a frequency signal 10 times the frequency difference, that is, a frequency signal of 1 MHz × 10 = 10 MHz.

  A filter 71 is connected to the subsequent stage of the amplifier 5 via a matching circuit 6 including a capacitive element 61 and a resistive element 62. This filter 71 targets the frequency signal multiplied by 10 described above, that is, a frequency signal of 10 MHz, and allows only a frequency signal of 10 MHz to pass through. An amplifier 72 that forms an amplifying unit and a counter 73 that is a counting unit are connected to the subsequent stage of the filter 71, and a data processing unit 74 that performs data processing based on the count value is provided to the subsequent stage of the counter 73. .

  Next, the operation of the above embodiment will be described. When the crystal unit 11 is immersed in, for example, pure water, it oscillates in a state where the oscillation frequency is slightly lower than that in the atmosphere due to the adhesion of pure water to the crystal surface. Here, when this frequency is assumed to be 9 MHz, the heterodyne detector 3 takes out a frequency signal of 1 MHz that is a frequency difference between a 10 MHz frequency signal that is a reference frequency and a 9 MHz frequency signal from the oscillation circuit 13, and supplies it to the low pass filter 4. The noise is removed and the 1 MHz frequency signal is passed. This frequency signal is input to the amplifier 5 and the amplifier 5 amplifies the frequency signal. In this case, since the signal input to the amplifier 5 is a sine wave, harmonics are generated at the same time. This harmonic includes a frequency signal of 10 MHz, which is a harmonic of 10 times the frequency of 1 MHz. When the frequency signal from the amplifier 5 is passed through the filter 71, the filter 71 is configured to pass the 10 MHz frequency signal, so that the 10 MHz frequency signal is extracted from the filter 71. The 10 MHz frequency signal is amplified through an amplifier 72, and the amplified frequency signal is counted by a counter 73.

  Further, the frequency difference output means is not limited to the heterodyne detector 3 and may be one that digitally extracts the frequency signal of the frequency difference. Even when the frequency signal is a rectangular wave, the low-pass filter 4 Since the waveform is blunt when a 1 MHz frequency signal passes, harmonics are also generated when the frequency signal passes through the amplifier 5, and a 10-fold frequency signal is obtained.

  In the data processing unit 74, for example, if the measurement time is set to 1 second, the count value for 1 second is stored, and this is set as a blank value. As this blank value, for example, count values for 1 second are sequentially stored, and an average value of the time series values may be used. Alternatively, a count value at the time when the count value is stabilized may be used. The blank value may be obtained in advance and stored and used. Here, in order to facilitate the description, the description will be made assuming that the stored blank value is 10 MHz.

  Now, when a sensing object, for example, a solution containing dioxin is supplied into the solution 12 in the container 10 and stirred, the dioxin is selectively captured by the adsorption layer made of antibodies on the surface of the crystal unit 11, The resonance frequency (natural frequency) of the crystal unit 11 changes by Δf according to the amount of adsorption. For this reason, the oscillation frequency from the oscillation circuit 13 is 9 MHz−Δf, and therefore the frequency of the frequency signal from the heterodyne detector 3 is 1 MHz + Δf. Since this frequency is multiplied by 10 as described above, it becomes 10 MHz + 10Δf and is counted by the counter 73. For example, when the measurement time is 1 second, the data processing unit 74 compares 10 MHz + 10Δf, which is a count value for 1 second, with, for example, 10 MHz, which is a blank value stored in advance, and 10Δf is obtained as a change in frequency. It is done.

  If Δf is 0.1 Hz, the resonance frequency of the crystal unit 11 changes from 9,000,000 Hz to 8,999,999.9 Hz as shown in FIG. The frequency difference is 1,000,000.1 Hz. If the frequency difference is counted as it is without being multiplied by 10 as in the present invention, the minimum unit of counting in the counter 73 is 1 pulse. Therefore, when this frequency difference is counted, as shown in FIG. It takes 10 seconds for 1 Hz to appear as one pulse.

  On the other hand, when the frequency difference is multiplied by 10, the frequency input to the counter 73 is 10 MHz + 10Δf, that is, 10,000,001 Hz. Therefore, the time required to count the frequency difference is as shown in FIG. 1 second. Then, in the data processing unit 24, when the count value is compared with the blank value described above, it is possible to detect a change of 1 Hz that is 10Δf. The change of the frequency multiplied by 10 is 1 Hz (1 Hz is increased) means that the frequency of the crystal unit 11 is reduced by 0.1 Hz, and the change of 0.1 Hz in the 9 MHz crystal unit 11 is changed. The minute could be detected. When the change in frequency can be detected in this way, for example, the concentration of dioxin in a solution in which the quartz crystal resonator 11 is immersed can be known based on a calibration curve prepared in advance, and therefore the measurement supplied into the container 10 is obtained. The dioxin concentration in the target solution can be detected. This density is displayed on a display means (not shown). In this example, the data processing unit 74 corresponds to a means for detecting a sensing substance by detecting a change in frequency.

  This sensing device may be configured as a concentration sensor that displays the dioxin concentration. However, the detected frequency change is compared with a preset threshold, and if it is lower than the threshold, it is determined that there is no dioxin. If it is higher than that, a means for determining that dioxin is present may be provided to constitute a presence sensor for displaying whether dioxin is present.

In the above example, the measurement time is 1 second, but it may be 10 seconds. In this case, it is possible to detect a change of 0.01 Hz with respect to the frequency change of the crystal unit 11, and the frequency change rate is approximately 10 ⁻⁸ , which corresponds to the adsorption of 10 picograms. Can be detected. For example, measurement sensitivity can be extended from nanogram to picogram levels. In this case, in the configuration in which the multiplication is not performed by 10, it takes 100 seconds for the counter 73 to recognize the change. For example, when a large number of samples are inspected as an actual apparatus, it takes a considerably long time. End up.

  That is, the sensing device according to this embodiment has an effect that measurement can be performed in a short time while obtaining high resolution. By the way, if only such an effect is aimed, the oscillation frequency of the crystal resonator may be set to 90 MHz which is 10 times 9 MHz. In that case, a counter 73 capable of counting 90 MHz must be used. Becomes complicated and the source of the clock becomes quite expensive, which is not realistic. In contrast, in this embodiment, the oscillation frequency of the crystal unit 11 is once beat-down, that is, dropped from 9 MHz to 1 MHz, and the frequency signal of 1 MHz is multiplied by 10. Therefore, a simple counter 73 is used. Can be used.

  Note that the oscillation frequency of the crystal unit is not limited to 9 MHz, but preferably, for example, 5 MHz to 155 MHz. Further, the multiplication number is not limited to 10 multiplication.

  In the present invention, the crystal resonator 11 is not limited to being immersed in the solution, and the solution may be hung on the surface of the crystal resonator 11, and environmental pollutants other than dioxins such as PCB (polychlorinated biphenyl). It may be one that senses or the like, or one that senses a virus, or one that senses a marker protein or the like. Furthermore, the present invention is not limited to sensing substances present in a liquid, but may sense substances present in the atmosphere, such as oil odor detection, fire smoke detection, or sarin gas. It can be applied in various fields such as detection of poisonous gas such as, detection of gas in parts, and detection of gas in a clean room such as a semiconductor manufacturing factory.

In order to confirm the effect of the apparatus of the present invention, the following experiment was conducted. An electrode having a two-layer structure of chromium and gold is formed on both surfaces of an AT-cut crystal piece, and one of the surfaces is sealed to form a Langevin type crystal resonator, and an electrode formed on an unsealed surface On the surface, an antibody obtained from a mouse was applied in a thickness of about 50 mm to form an adsorption layer. The crystal resonator (crystal sensor) thus manufactured is incorporated in the sensing device of the embodiment of FIG. 1, the crystal resonator is immersed in ultrapure water, and the oscillation frequency F1 is set to 9 MHz by the counter 73. And measured to the order of 0.1 Hz. Subsequently, the antigen obtained from the goat was put in this ultrapure water, and the oscillation frequency F2 was similarly measured to the order of 0.1 Hz. F2 was 0.5 Hz lower than F1. When this is expressed by the frequency change rate of the following formula (1),
df / f = (F2-F1) / F1 (1)
The change rate is 0.055 ppm because F1 is about 9 MHz. Therefore, a minute change in frequency can be read in one second.

It is a block diagram which shows the whole structure of embodiment of the sensing apparatus which concerns on this invention. It is explanatory drawing which shows the change of the oscillation frequency of a crystal oscillator. It is explanatory drawing which shows the time length in the case of counting, without multiplying by 10 like this invention, when the oscillation frequency of a crystal oscillator changes. It is explanatory drawing which shows the time length in the case of counting by multiplying 10 like an embodiment, when the oscillation frequency of a crystal oscillator changes.

Explanation of symbols

DESCRIPTION OF SYMBOLS 11 Crystal oscillator 13 Oscillation circuit 2 Reference frequency generation part 3 Heterodyne detector 4 Low pass filter 5 Amplifier 71 Filter 72 Amplifier 73 Counter

Claims (3)

An adsorption layer for adsorbing the sensing object is formed on the surface thereof, and a sensor vibrator whose natural frequency is changed by the adsorption of the sensing object is used, and the sensing object is detected by a change in the natural frequency of the sensor vibrator. In the sensing device that senses
An oscillation circuit for oscillating the sensor vibrator;
A reference frequency generator for generating a reference frequency signal;
A frequency difference output means for extracting a frequency difference between the frequency signal from the oscillation circuit and the reference frequency signal and outputting a frequency signal of the frequency difference;
Multiplication means for multiplying the frequency signal of the frequency difference;
A sensing device comprising: counting means for counting frequency signals multiplied by the multiplication means. A low-pass filter that allows the frequency signal of the frequency difference to pass after the frequency difference output means is provided,
2. The multiplication means comprises an amplifying unit that amplifies the frequency signal that has passed through the low-pass filter and outputs a signal including a harmonic corresponding to the frequency signal obtained by multiplying the frequency signal. Sensing device. 3. The sensing device according to claim 1, further comprising a filter that allows the frequency signal multiplied by the multiplication means to pass after the multiplication means.

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