KR20000070358A - QCM Sensor - Google Patents

Abstract

A QCM sensor that detects and quantifies a component of a sample from a change in main resonance frequency or a change in impedance when the electrode surface of a sensor device having electrodes disposed on the front and rear surfaces of a quartz substrate is immersed in a sample gas or a sample solution.

The sensor device is a multi-channel structure in which four counter electrodes 11A to 14A and 12B to 14B are provided on the front and rear surfaces of the quartz substrate 10, and it is preferable to fix different receptors for each component of the sample to be detected and quantified on each electrode. As a possible structure, different components are detected and quantified at once in one sample.

Description

QCM Sensor

It is important to quantify the amount of reaction or product in the field of chemistry and biochemistry. However, it is difficult to obtain sufficient detection sensitivity for a very small amount of reaction.

Chemical and biochemical sensors using the microplasma principle using AT-Cut crystal oscillators have been developed and attracting attention.

The crystal oscillator of AT-cut has the main resonant frequency in inverse proportion to the plate thickness of the oscillator. In this case, when a sample component is deposited on the electrode face of the crystal oscillator or when the adsorption of material occurs on the electrode face steel, a frequency shift occurs corresponding to the weight of the material present on the surface per unit plane.

QCM sensor is the application of the frequency shift phenomenon. The crystal oscillator of AT-cut can expect stable detection sensitivity because the frequency characteristic is stable over wide temperature range. Once the conditions are set, detection of 1 to 10 ng of adsorbate in real time is possible.

The relationship between the absorbed material amount and the frequency shift amount is described below.

First, the vibration frequency of the AT-cut crystal oscillator is shown in equations (1) and (2) shown in FIG.

In each of equations (1) and (2), f _o is the principal resonant frequency of the crystal oscillator, ν is the sound velocity in the crystal, t _q is the thickness of the crystal, μ _{q is the} shear modulus of elasticity, and ρ _q is the crystal density. .

The mass change Δm occurring on the surface of the crystal oscillator having the main resonance frequency f _o is developed as shown in Equation (3) shown in FIG. 13 by developing a relation between the main resonance frequency and the thickness of the crystal.

In the above Equation (3), Δf represents the frequency change by the mass addition, A _piezo represents the electrical effective area, and C _f represents the overall sensitivity.

The crystal oscillator having the main resonance frequency f _o of Equation (3) can be rewritten as Equation (4) shown in Fig. 14 since Δf is affected by the viscosity and density of the liquid.

η _L represents the viscosity of the solution and ρ _L represents the density of the solution and ω _o = 2πf _o .

In addition, the total sensitivity C _f is expressed by equation (5) in FIG.

As can be seen from Equation (5), it is important to increase the main resonance frequency f _o to increase the overall sensitivity C _f . The overall sensitivity C _f itself is a function of frequency, and the deviation Δf of the frequency actually depends on the 3/2 square of the main resonant frequency f _o .

Therefore, if the main resonance frequency of the crystal oscillator used as the sensor is high, a high sensitivity sensor can be used. For example, FIG. 16 is a characteristic graph showing the frequency shift amount Δf of a crystal oscillator contained in a 15 wt% (wt%) glucose solution. It can be seen that as the main resonance frequency f _o increases, the deviation of the resonance frequency increases with respect to the adsorption amount of the same electrode surface.

As described above, since the AT-cut crystal oscillator uses the thickness-slip mode, the main resonance frequency f _o is inversely proportional to its thickness t _q . In addition, the electrode effective area is proportional to the frequency in order to obtain a sufficient value γ (γ represents the ratio of parallel capacitance and series capacitance in the equivalent circuit of the crystal oscillator, which is usually about 250 in the case of an AT-cut crystal oscillator). It needs to be small.

For the above reasons, a crystal oscillator used for high frequency needs to provide a crystal oscillator having a small electrode area and a thin crystal thickness.

On the other hand, in order to realize the QCM sensor, as shown in Fig. 17, the crystal oscillator 1 is held in the container 2, and only the vibrator surface is exposed to be immersed in the sample, and the periphery thereof is sealed with an O-ring 3 or the like. And a device connected to the oscillation circuit or the impedance measuring circuit 4 by using the lead wires from the crystal oscillator electrodes 1A and 1B.

Since the QCM sensor having the above-described configuration has a thin crystal substrate according to the crystal oscillator for high frequency, the substrate is often distorted (tensioned) or broken by the stress applied to the sealing portion.

Therefore, it is difficult to apply the sensor device to high frequency. However, a method of manufacturing a QCM sensor device has been proposed by Zuxuan Lin et al. To etch a single cell to thin only a central portion of a substrate.

In this case, the part corresponding to the frame of the crystal oscillator has a thickness of 5 to 6 MHz (0.3 mm equivalent), which is conventionally used, and no large distortion of the part due to sealing occurs. In addition, the thinned portion is small enough to provide an energy trap so that it is difficult to be affected by the mold.

The QCM sensor for increasing the sensitivity can be achieved by the above method, but the conventional QCM sensor is configured so that only one sensor is in one cell. Thus, conventional sensors perform one component measurement at a time on one sample.

For example, in order to detect and quantify each component in a sample solution containing a plurality of components, it is to measure each component of a limited sample called 1-cell-1-sample that can detect and measure each cell. . As a result, conventional QCM sensors take a long time to measure individual components and are expensive to measure.

To shorten the measurement time, a multi-channel QCM sensor has been proposed. The multi-channel QCM sensor is configured as follows. A number of vibration modifiers are attached on the substrate holder and the probe moves over each crystal oscillator and data for each component of the sample is obtained for each crystal oscillator.

However, in the multi-channel QCM sensor, the application of an electric field occurs by the movement of the probe.

The deviation of the probe's relative position with respect to each crystal oscillator changes the oscillation frequency and impedance.

Conventional multi-channel QCM sensors are difficult to actually configure to accurately maintain measurement conditions, such as the resonance frequency of a crystal oscillator.

In addition, conventional QCM sensors are unable to obtain stable measurements as a result.

Accordingly, an object of the present invention is to provide a QCM sensor having a multi-channel structure in which the sensor unit can stably measure each component of the sample and high frequency measurement by increasing the main resonance frequency of the sensor unit.

The present invention is directed to a QCM (Quartz Crystal Microbalance) sensor that detects and quantifies (quantitatively analyzes) a component of a sample from a change in oscillation frequency or impedance of the crystal oscillator when the electrode surface of the crystal oscillator is immersed in the sample gas or the sample solution. The invention relates in particular to a multi-channel QCM sensor suitable for detecting and quantifying a plurality of components from the same sample.

1A and 1B are a plan view and a side view of a sensor device according to a first embodiment.

Fig. 2 is a table showing a distance at which sufficient mechanical vibration attenuation can be obtained at a ratio L / t of the crystal thickness t to the resonance frequency f _o and the distance L from the end of the electrode to the end of the adjacent electrode.

3 is a side view of a sensor device according to a third embodiment of the present invention.

Figure 4 is a graph of the deviation characteristics of the measured frequency when the separation groove is installed.

Fig. 5 is a side view of the sensor device of the fourth embodiment according to the present invention.

6 is a plan view of a sensor device used in an experiment of mutual interference between electrodes.

7 is a silver precipitation apparatus used in the mutual interference experiment between the electrodes.

8 is a characteristic diagram showing the frequency change ΔF for each channel in the mutual interference experiment between the electrodes.

9 is a characteristic diagram showing series resonance resistance for each channel in the mutual interference experiment between electrodes.

FIG. 10 is a chart showing changes in frequency and series resonant resistance when water droplets are dropped onto a channel in an interfering experiment between electrodes.

11 is a side view of a sensor device according to a fifth embodiment of the present invention.

12 are equations (1) and (2) for the resonance frequency of an AT-cut crystal oscillator.

Fig. 13 is a formula showing a frequency change by correction.

Fig. 14 is a formula showing a frequency change when a crystal oscillator is used in a liquid.

Fig. 15 is a formula showing overall sensitivity.

Fig. 16 is a characteristic diagram showing frequency dependency of sensor device sensitivity.

Fig. 17 is an example of device configuration of a conventional QCM sensor.

The sensor device according to the present invention has a structure in which the ratio L / t between the quartz substrate thickness t and the distance L between adjacent electrodes is 20 or more if the electrode of the multi-channel structure is circular.

According to the above structure, high-precision measurement is possible without mutual interference between adjacent electrodes, and thus it is possible to detect and quantify different components for each electrode at a time with one sample and to reduce the overall size of the sensor device.

The sensor device according to the present invention is a multi-channel structure in which electrodes are arranged adjacent to each other, and each electrode has a structure in which different receptors are fixed to each component of a sample to be detected and quantified. Since the probe does not need to move in the conventional multi-channel QCM sensor, stable measurement can be performed without changing the measurement conditions.

In addition, the device structure is simple because only the sensor device and the measuring device.

The quartz crystal substrate of the sensor device according to the present invention is provided with a separation groove for lowering vibration energy between adjacent electrodes. The structure attenuates the leakage of vibration energy between the electrodes with a separation groove to shorten the distance between the electrodes to obtain a stable measurement measurement frequency.

The quartz substrate of the sensor device according to the present invention has a structure in which the thickness of the electrode forming portion is thinner than the thickness of the peripheral portion.

The modified substrate of the sensor device according to the present invention can be used in a high frequency range by improving the mechanical strength of the substrate to ensure its retention and to reduce the thickness of the electrode portion.

The sensor device according to the present invention is a substrate holder made of a quartz substrate or a quartz substrate on which an electrode forming portion using a thin quartz substrate for high frequency is thinner than the thickness of the peripheral portion and a sensor device body, to which the sensor device body is attached. It consists of.

According to the above configuration, in order to prevent the quartz substrate from cracking, the amount of etching for thinning the electrode portion must be reduced in order to increase the frequency of the sensor device.

The sensor device according to the present invention may use Langasite quartz having a large mechanical coupling coefficient instead of the quartz substrate.

(First embodiment)

1A and 1B show a plan view and a side view of a multi-channel QCM sensor of a first embodiment according to the present invention.

The quartz crystal substrate 10 is composed of an AT-cut crystal having a uniform thickness in a rectangular shape. Circular electrodes 11A, 12A, 13A, 14A and 11B, 12B, 13B, 14B (made of gold or platinum, respectively) are mutually formed on the front or rear surface of the quartz substrate 10 by a sputtering method. 14A at each electrode 11A and 14B at 11B are drawn out at the terminals around the quartz substrate by 18A at lead wires 15A and 18B at 15B, respectively.

The thickness of the quartz substrate 10 is determined according to the main resonance frequency f _o (5 MHz or 10 MHz) in equations (1) and (2). In addition, the area of each electrode is determined as an element which determines the sensitivity of Formula (5) in Formula (3).

In order to configure the QCM sensor using the above-described sensor device, as shown in Fig. 17, one surface of the front or rear surface is immersed in the sample. Depending on the components to be detected and quantified (quantitative), different receptors are formed on one of the front or rear surfaces of the electrodes 11A-14A.

For example, anti-measles virus for detecting and quantifying measles virus is immobilized on electrode 11A and the pandemic antigen for detecting and quantifying pandemic antibodies is immobilized on counter electrode 11B.

In addition, each of the electrodes 11A to 14A and 11B to 14B is connected to an individual oscillation circuit or an impedance measurement circuit or is switched to a single oscillation circuit in a time division mode.

Therefore, when the electrodes 11A to 14A are contained in the sample, the vibration frequency or the impedance change is measured separately.

In the sensor device having the above-described configuration and the QCM sensor in which the sensor device is used, each electrode 11A to 14A is connected to the same sample. However, it is possible to detect and quantify different components at once in one sample for each electrode. In the case of the configuration shown in Figures 1A and 1B, four components in one sample can be detected and quantified at once.

In addition, since the probe movement operation is unnecessary in the conventional multi-channel type QCM sensor, stable measurement can be performed without changing the measurement conditions. Furthermore, the device configuration is a simple configuration in which the sensor device only needs to be connected to one or each measuring device.

(Second embodiment)

In the multi-channel structured sensor device shown in FIGS. 1A and 1B, vibration energy coupling occurs between adjacent electrodes, and thus it is not necessary to provide sufficient space between the electrodes. A detailed analysis of energy constraints by electrodes formed on crystal oscillators was done by William Shokley et al.

In the second embodiment, a structure in which the electrode film thickness is made sufficient so that mutual interference between adjacent electrodes does not occur, and the distance between adjacent electrodes which sufficiently restricts the main resonance on the electrode is limited to the numerical value or more shown in FIG. Have

In Fig. 2, at a distance L from the electrode end to the end of the adjacent electrode and the ratio L / t to the crystal thickness t, the distance at which sufficient mechanical vibration damping is obtained is defined.

In the second embodiment, the ratio L / t is 20 or more in the case of a circular electrode.

According to the QCM sensor using the sensor device under the above conditions, it is possible to measure a fixed bill without mutual interference between adjacent electrodes and reduce the size of the entire sensor device.

(Third embodiment)

As described above, in the case of the multi-channel QCM sensor shown in the first sealing example, it is necessary to take sufficient inter-electrode distance between the electrodes in order to eliminate mutual interference. Therefore, the overall size of the sensor device is increased. Next, although the size becomes small, the size limitation is made within the range described in the second embodiment.

Figure 3 shows a side view of a sensor device in a third embodiment according to the present invention.

In the third embodiment, each separation groove 20 is provided between each electrode and the adjacent electrode to contain the vibration energy. As a result, mechanical vibration leakage between each channel is reduced.

Stabilization of the frequency under measurement can be achieved by installing the separation groove 20. Figure 4 shows the deviation of the measurement by the repetition of the measurement frequency for the sensor device of the structure without the separation groove and the structure formed with the separation groove 20. It can be seen that the separation is reduced in the case of the sensor device having the separation groove.

Therefore, since each separation groove 20 helps to forcibly attenuate mechanical vibration, it is possible to shorten the distance between electrodes as compared with the sensor device of the first or second embodiment. The sensor device can be miniaturized.

Furthermore, in the case where the QCM sensor is used in the solution system, as shown in Fig. 17, a method of waterproofing using an O-ring is performed on the quartz substrate. There is a possibility that the quartz substrate may be distorted by the force of the O-ring that presses the quartz crystal substrate of the sensor device without the separation groove and the vibration frequency may move (toward the high frequency). However, in the third embodiment, the separation groove can be effectively operated so that no frequency shift occurs with respect to the phenomenon.

Further, although the third embodiment can be applied to the multi-channel structure of the first embodiment, mutual interference can be reliably reduced by the structure of the third embodiment in combination with the conditions of the second embodiment.

(Example 4)

In the first and third embodiments, the sensor device has a main resonance frequency of approximately 5 MHz. In the case described in the third embodiment, this is because a shield is performed to separate the sample atmosphere from the measurement circuit portion. In this case, a substrate thickness of at least 0.25 mm is required to reduce cracks and reduce deformation (distortion) of the quartz substrate.

On the other hand, as described in the background, it is necessary to use a high frequency oscillator having a thin thickness in order to obtain a high sensitivity sensor.

In the fourth embodiment, as shown in Fig. 5, the periphery of the quartz substrate 10 is thickened with a multi-channel sensor to secure the mechanical strength and thin the vibrator portion on which the electrodes 21A, 21B, 21C, and 21D are formed. This enables high frequency applications.

For example, each electrode film formed on the one square inch substrate portion is etched to a thickness such that the main resonance frequency is 10 MHz or more.

In the above example, since the thickness of the electrode portion is made thin, the distance between the electrodes can be further reduced for the miniaturization of the sensor device, and the mutual interference between the electrodes can be further reduced.

The QCM sensor device of the fourth embodiment was manufactured in a circle having a frequency of the vibrator portion in the range of 10 to 150 MHz.

The distance between the electrodes is shortened to the value shown in the second embodiment or shorter than the value shown in the second embodiment.

For example, even if the ratio of the distance L from the electrode end to the adjacent electrode end and the thickness t of the quartz substrate is set to 16 or less, no cross-frequency interference was observed in the sensor device with a vibration frequency of 10 MHz.

An experiment was conducted to verify that the sensor device of the embodiment is used to measure frequency variation and series resonance resistance without mutual interference between channels.

The sensor device used in the experiment was formed with four channels from CH1 to CH4 as shown in FIG.

The sensor device embeds a quartz substrate into two gold electrodes. The substrate size is 200 square mm and the thickness is 267 μm. The gold electrode periphery on the front or back is dug into a 8.0 mm diameter and 50 μm deep by wet etching. The thickness of each electrode part is 167 μm and the main resonant frequency f _o is 10 MHz.

To each gold electrode, chromium was coated on the quartz substrate to bond gold to the quartz substrate and gold was deposited to 1000 angstroms and 4.5 mm in diameter, and each gold lead wire was 0.5 mm wide.

This type of sensor device, as shown in FIG. 7, has 1 × 10 ⁻³ moles of acetic acid attached to the bottom of vessel A and containing 0.2 moles of perchloric acid (HClO ₄ ) as a supporting salt in the vessel. (AgNO ₃ ) A multi-channel quartz crystal electrolytic cell is constructed in which an aqueous solution is put in, a sensor device as a working electrode, a counter electrode of platinum wire, and a gold wire as a reference electrode.

In using the electrolytic cell, constant current electrolysis of 1 mu A is performed for each electrode of the sensor device. Then, silver precipitates. When silver was deposited at each electrode, the frequency change ΔF (Hz) of the channel CH1 and the series resonance resistance R ₁ ( ₁ ) were measured. In the above experiment, as shown in FIG. 8, the frequency change ΔF (Hz) was large when silver precipitated in the channel CH1 and extremely small when silver precipitated in the channel CH2.

9 shows the series resonance resistance change. In this case, the resistance change R ₁ was large when silver precipitated in the channel CH1.

However, when silver precipitated in other channels CH2 to CH4, the resistance change was extremely small.

In the above fact, it can be seen that each channel of the 4-channel sensor device is independent of each other and can be detected and quantitatively measured for each channel without causing mutual interference.

As another experiment to prove that mutual interference between each channel is eliminated, the frequency change ΔF and the series resonance resistance R ₁ when 70 μl (microliter) of water droplets are put on each channel of the 4-channel sensor device shown in FIG. Was measured.

The results are obtained as shown in the table of FIG.

As can be seen from the above table, the frequency change and the resonance resistance change are remarkable when the water droplet is placed only on the channel CH1.

When water droplets are placed from CH2 to CH4, the frequency change of CH1 is less than 1% and the resistance is less than 2%, so that almost no frequency and resistance change occurs.

According to the result, each channel is independent and can detect and quantify without causing mutual interference.

In addition, the sensor device of the fourth embodiment is applicable to the multi-channel structure of the first embodiment, and a combination of the respective separation grooves of the third embodiment can be obtained.

(Example 5)

In the QCM sensor of the fifth embodiment, the etching process of the quartz substrate at approximately 6 MHz was made thin for high frequency application.

When the frequency is 50 MHz or more, the etching amount reaches 244 μm.

Therefore, when it takes a long time to perform the etching, it can be predicted that a frequency error between each channel or between individual sensor devices will occur at the same time.

In the embodiment shown in Fig. 11, an electrode 30B is formed at a portion which is etched into a predetermined thickness by etching a thin quartz crystal substrate 30A for a high frequency of about 80 mu m. The sensor device main body 30 is attached to a quartz substrate 31 (or a quartz substrate) of approximately 250 µm in order to form the quartz substrate 31 as a substrate holder.

It is preferable to use a flexible material having a low modulus of elasticity as an adhesive for adhering the sensor device main body 30 onto the quartz substrate in order to minimize the stress to the electrode portion and its periphery as much as possible.

In the fifth embodiment, etching of a relatively thin quartz crystal substrate is performed to manufacture a high-frequency sensor device, and the etching time can be shortened and the variation in etching amount can be eliminated.

The fifth embodiment can be applied to the fourth embodiment and the sensor device main body can have a structure having a separation groove of the third embodiment.

In each embodiment, the material of each electrode is made of gold. However, it is possible to use a gold-chromium electrode having a chromium layer of 50 angstroms to 500 angstroms between the quartz substrate and the gold electrode as the electrode material.

It is also possible to use titanium or nickel instead of chromium.

Further, in each embodiment, the number of electrodes is four and the number of channels is four.

However, in recent years, an artificial crystal with a diameter of 100 mm is being grown by growing a longitudinal crystal by hydrothermal synthesis at high temperature and high pressure in an elongated autograve made of special steel. Thus, in the QCM sensor device of each embodiment, for example, a large quartz substrate having a diameter of 100 mm can be used with a plurality of electrodes capable of arranging a plurality of electrodes.

Moreover, it is not necessary to have an electrode area formed on the same front surface as the electrode formed on the back surface.

In each embodiment, the quartz substrate is used as the substrate. Langasite modifications with high mechanical coupling coefficients may be used.

As described above, the QCM sensor according to the present invention is stable to obtain a multi-channel sensor device that immerses the sensor device in a sample gas or a sample solution to detect and quantify the components of the sample and detects and quantifies the components in one sample at a time. It is suitable as a sensor used for measurement and high frequency measurement.

Claims (6)

Detecting and quantitatively analyzing the components of the sample from the change of the main resonance frequency or the impedance when the electrode device of the sensor device is disposed on the front and rear surfaces of the quartz substrate and the electrode surface of the sensor device is immersed in the sample gas or the sample solution. In the QCM sensor, The sensor device has a multi-channel structure in which a plurality of electrodes are provided adjacent to the front and rear surfaces of the quartz substrate, respectively, and each of the electrodes has a structure capable of fixing different receptors for each component of the sample to be detected and quantified. QCM sensor. The method of claim 1, The QCM sensor is characterized in that the electrode of the sensor device is almost circular and the ratio L / t of the distance L between each electrode and the adjacent electrode on the same surface and the thickness t of the quartz substrate is set to 20 or more. . The method of claim 1, The sensor device has a QCM sensor, characterized in that the separation groove is provided between the electrode on the same plane and the adjacent electrode in order to lower the vibration energy coupling between the adjacent electrodes. The method of claim 1, The quartz crystal substrate of the sensor device is characterized in that the thickness of the electrode forming portion is thinner than the thickness of the peripheral portion of the QCM sensor. The method of claim 3, wherein The sensor device includes a sensor device main body having a thickness of each electrode forming part thinner than a peripheral part using a thin quartz substrate for high frequency, and a crystal substrate having a thickness thicker than that of the sensor device main body and to which the sensor device main body is attached. Or a substrate holder made of a quartz substrate. The method of claim 1, The sensor device is a QCM sensor, characterized in that using a Langasite crystal having a large mechanical coupling coefficient in place of the quartz substrate.