JP4216692B2 - Mass sensor - Google Patents

Description

The present invention uses QCM (Quartz), which uses “Sauerbrey's theory” that measures the change in mass by the magnitude of frequency change when various minute masses (objects) intervening on a piezoelectric single crystal substrate are desorbed. The present invention relates to a crystal micro-balance type mass sensor.

  In recent years, research on global environmental pollution problems and human genetic elucidation has been conducted. For example, identification of environmental hormone species, antigen-antibody reaction, binding of high molecular proteins (DNA-DNA, DNA-RNA) Reactions, analysis of enzyme reactions, proteome analysis, etc. are actively performed. And as these analytical techniques, apparatuses such as a gas chromatography mass spectrometer (GC-MS), a high performance liquid chromatograph (HPLC), and a surface plasmon resonance measuring apparatus (SPR) are used. These instruments are large and expensive equipment, and at the same time have a very high analytical sensitivity, but they require a lot of labor and time for sample preparation, and it is difficult to analyze multiple components simultaneously. There's a problem. In addition, there is always a demand to observe the reaction process in real time, but this is not possible with the equipment described above.

  When a complementary binding reaction such as an antigen-antibody reaction or DNA-RNA binding occurs, a change in weight or a change in dielectric constant occurs. With the QCM mass sensor, it is possible to capture such minute changes. In a mass sensor using a piezoelectric single crystal as a sensor element, ng (nanogram) level weight measurement is possible. By immobilizing an antibody (or antigen) on the device surface, the antigen (or antibody) The reaction can be detected. In addition, regarding the PH value (the common logarithm of the reciprocal of the hydrogen ion concentration expressed in terms of molar concentration) and the conductivity, it is also possible to detect a change in conductivity by an acoustoelectric interaction. Furthermore, since the process of reaction can be grasped as frequency change, real-time quantitative analysis can be performed by measuring and recording the state of frequency change in real time. FIG. 3 shows the structure of a mass sensor element used conventionally.

(1) N. Miura, H. Higabashi, G. Sakai et al .: Piezoelectric crystal immunosensor for sensitive detection of methamphetamine (stimulant drug) in human urine Proc. Fourth Int. Meeting on Chemical Sensors, Technical Digest, Tokyo. Pp. 13- 17 (1992)

  The QCM mass sensor uses a phenomenon in which the frequency fluctuates in proportion to a change in mass on a piezoelectric single crystal substrate having a finite dimension that is performing natural vibration in a specific vibration mode. Now, when a piezoelectric single crystal is described as a quartz crystal, the sensitivity to the change in mass of the quartz crystal element is extremely high. Since a minute mass change can be observed as a frequency change, it is used as a sensor for measuring a minute mass change.

  Therefore, the QCM mass sensor is used by exposing the sensor element substrate surface in a gas phase or liquid phase atmosphere depending on the environment of the object to be measured. Need to be reflected in frequency changes. During measurement, it is necessary to eliminate as much as possible the influence of external disturbances such as contamination of the sensor element surface due to adhesion of substances other than the object to be measured and environmental temperature changes. In addition, since the QCM mass sensor directly reads minute mass changes as frequency changes, it is necessary to keep the initial fluctuation of the oscillation frequency derived from the crystal sensor element / oscillation circuit and the frequency drift to the minimum (stable state). For this purpose, it is important to maintain the drive voltage necessary for excitation of the sensor element at a minimum value at which oscillation can be stably maintained in the environment and the vibration amplitude at a constant value.

  Therefore, if the drive voltage is controlled and the sensor element is excited with low drive and constant amplitude, the mechanical distortion abnormality due to excessive vibration due to excessive drive voltage and self-heating inside the sensor element, initial frequency fluctuation, It is possible to minimize the effects of viscous fluids such as viscosity and specific gravity regardless of the gas-phase or liquid-phase environment, preventing the frequency drift phenomenon, improving the disturbance caused by the sensor element and observing immediately after the start of oscillation. The initial fluctuation phenomenon of the frequency to be measured and the frequency stability during measurement are improved. Further, in the measurement of the QCM mass sensor, a wide variety of minute mass changes are measured (can be performed), and thus an appropriate drive voltage that matches the non-measurement substance is required. Therefore, in the mass sensor of this patent, a reference voltage circuit is provided so that the drive voltage can be controlled from the outside, and at the start of measurement, the reference voltage is intentionally and flexibly adjusted to provide an appropriate drive voltage for the object to be measured. The vibration amplitude is controlled from the charge amount obtained by the monitor electrode provided adjacent to the excitation electrode on the sensor element substrate so that the vibration amplitude is always set during measurement.

  Since the QCM mass sensor directly reads a minute mass change as a frequency change, it is necessary to keep the initial fluctuation of the oscillation frequency derived from the crystal sensor element / oscillation circuit and the frequency drift to the minimum (stable state). For this purpose, the drive voltage required for excitation of the sensor element is set to the appropriate and minimum voltage that can maintain stable vibration in the gas / liquid phase measurement environment, and the amplitude of the vibration becomes a constant value. This is an important point. Since the QCM mass sensor measures minute mass changes due to various bonds and reactions, an appropriate drive voltage according to the non-measurement substance is required. In order to realize these, the present invention is characterized in that a monitor electrode is provided on the substrate of the sensor element independently of the excitation electrode, and the amount of electric charge generated at this electrode is controlled to be always constant.

  Normally, to control the amplitude of a crystal resonator, the voltage generated at the output terminal of the crystal resonator is treated as a monitor signal, this signal is introduced into an AGC circuit, etc., and the amplitude is kept constant by controlling the excitation voltage of the oscillator. The method of holding in the above is general. In the present invention, the reason why the monitor electrode for detecting the magnitude of the amplitude of the sensor element is provided independently is that the measurement environment is a viscous fluid (including gas phase and liquid phase), and the surface is exposed in the environment. As for the state of the amplitude of the sensor element placed, the method of converting the electrical signal after passing through mechanical vibration once to the electrical signal is more environmental conditions such as viscosity and specific gravity than using the electrical signal of the output terminal of the sensor element as the monitor signal. Therefore, it is possible to obtain a monitor signal with high accuracy that matches the actual situation.

  In addition, the appropriate value of the excitation condition differs between the exposed sensor elements due to changes in the viscosity and specific gravity of the measurement environment. Therefore, in the mass sensor of this patent, a reference voltage generation circuit that can vary the voltage is provided so that the appropriate drive voltage can be controlled from the outside, and the drive voltage is intentionally and flexibly adjusted at the start of measurement by this voltage. Set a drive voltage suitable for the object to be measured, so that the vibration amplitude generated by this drive voltage is always the same during measurement, that is, the amount of charge obtained by the monitor electrode on the sensor element substrate is constant. A structure that controls vibration amplitude is adopted.

FIG. 1 shows a sensor element of the present invention. The excitation electrode 2 is provided on the front and back surfaces of a piezoelectric single crystal substrate 1 using a rotating Y plate (for example, a piezoelectric material such as a quartz substrate and the shape of the main surface of the drawing is circular, but the shape is not limited to a circle). A monitor electrode 3 is arranged around the excitation electrode 2. In this excitation electrode 2 structure, a gold double thin film is deposited or sputtered on a titanium base, but other types of materials include chromium, nichrome, aluminum, etc. Titanium, aluminum, platinum black, SiO ₂ , copper, polystyrene, etc. are used. The monitor electrode 3 is charged with a parallel electric field generated in proportion to the amplitude of the vibration amplitude between the monitor electrode 3 and the excitation electrode 2 in the same plane due to vibration, and this is a monitor signal for controlling the amplitude of the sensor element. It becomes. Thus, the sensor element has a three-terminal structure. In addition, although the excitation electrode 2 formed on the front and back of the piezoelectric single crystal substrate 1 shown in FIG. 1 is composed of electrodes having substantially the same area, the electrode area of the excitation electrode 2 may be different.

  In FIG. 2, a circuit configuration example of the mass sensor will be described. The circuit can be largely divided into 4 parts. The first is an “excitation amplitude detector” that receives the monitor electrode terminal (M) of the sensor element, which is proportional to the vibration amplitude of the sensor element, and is an amplification circuit so that the amplitude becomes constant via the excitation gain control voltage. Adjust the gain. The second is a “control voltage generator for determining an excitation reference voltage” that determines an excitation gain of a reference (used as a bias) suitable for the measurement environment. Thirdly, in these two types of voltages, an “excitation gain control voltage generator” that multiplies “excitation amplitude detection voltage” by minus 1 with “control voltage for determining excitation reference voltage” as a reference, and Fourthly, an “oscillation circuit unit” that can vary the excitation gain by the “excitation gain control voltage”. The excitation circuit 2 terminals (S1) and (S2) of the sensor element are connected to the oscillation circuit unit, and the excitation gain is controlled so as to maintain the excitation amplitude set at the start of measurement without being caught by changes in the external environment. The

  Here, the operation of the above-described circuit configuration (FIG. 2) will be described. The QCM mass sensor normally uses an oscillation circuit and oscillates by connecting two terminals of the sensor element to the excitation electrodes S1 and S2. The signal from the S1 terminal converts current into voltage by an I / V conversion circuit. At that time, if the viscosity and specific gravity are different even in different measurement environments such as the gas phase, the liquid phase, and the liquid phase, the sensitivity conditions differ depending on the environmental change.

  In the present invention, when the monitor electrode is formed on the sensor element and the vibration propagates through the sensor substrate, the environmental condition is added and signal transmission is performed. Therefore, a signal (charge amount) with an environmental condition is generated at the monitor electrode terminal (M), and this charge amount is converted into a voltage by the Q / V conversion circuit, amplified and taken in, and noise is removed by a filter. After that, it is converted into a DC voltage by a rectifier circuit. The excitation gain is adjusted so that the DC voltage is constantly constant. As described above, since an appropriate excitation gain varies depending on the environmental conditions, a structure is adopted in which adjustment is performed from the outside so that the reference value is adapted by the excitation reference voltage control circuit.

  Although the monitor electrode is provided separately from the excitation signal system and is not drawn in the drawing, the monitor voltage (current) is affected by the measurement environment (viscosity, specific gravity, etc.), so it should be compared with the excitation signal. Since the phase difference can be confirmed with the above, the data obtained in advance for the phase difference state is stored in the memory circuit, and compared with the result of the monitor signal (M) and corrected to adjust the excitation amplitude according to the measurement environment. It is also possible.

  This sensor is used to measure mass changes in response to reactions and bonds in solution. For example, this sensor is also effective for measurements in the gas phase, such as measuring the content of environmental pollutants such as dioxins. It can be widely used for measurement of a wide variety of sensitive substances, facilitates work efficiency at the time of measurement, and improves the measurement accuracy as compared with the prior art.

It is the conceptual diagram which showed the external shape main surface (FIG. 1 (a)) of the sensor element of this patent, the example of sectional drawing (FIG.1 (b)), and the symbol notation (FIG.1 (c)). It is a block diagram which shows an example of the drive circuit structure of the mass sensor of this patent. It is the conceptual diagram which showed the external shape main surface (FIG. 3 (a)) of the conventional sensor element, the example of sectional drawing (FIG.3 (b)), and the symbol notation (FIG.3 (c)).

Explanation of symbols

1 Piezoelectric single crystal substrate 2 Excitation electrode 3 Monitor electrode

Claims (2)

Using a piezoelectric single crystal as a substrate, adding an excitation electrode and a monitor electrode for detecting the vibration state on the same substrate to convert the amount of charge into a voltage, and the amplitude of the mass sensor element excited by the excitation electrode In the mass sensor for recognizing the magnitude of the mass sensor, a circuit for controlling the excitation voltage is added so that the amount of charge collected by the monitor electrode or the monitor voltage becomes a constant value . 2. The mass sensor according to claim 1, wherein when the charge amount (converted voltage) is constant, the value is determined by a voltage value generated by a reference voltage circuit that can be varied from the outside.

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