Sensor device and frequency measurement method

Abstract

To provide a sensor device and a frequency measurement method, capable of supplying a sample to a crystal oscillator with a simple structure and reducing a size and weight.SOLUTION: A sensor device includes a crystal oscillator 15, a housing, a terminal part 42a, a mounting plate part 42 mounting the crystal oscillator 15, a frame body part 43 mounted on the mounting plate part 42, and a cover part 44 mounted on the frame body part 43. In the frame body part 43, a storage chamber 43a storing the crystal oscillator 15, and a sample inflow path 43b and a sample outflow path 43c which are grooves formed in communication with the storage chamber 43a are formed. In the cover part 44, an injection port 44b formed at a position corresponding to that of the sample inflow path 43b and an exhaust port 44c formed at a position corresponding to that of the sample outflow path 43c are formed.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] The present invention relates to a sensor device and a frequency measurement method, and more particularly to a sensor device and a frequency measurement method for measuring the mass of a sample using a change in the frequency of a quartz oscillator. [Background technology]

[0002] Conventionally, QCM (Quartz Crystal Microbalance) sensors have been proposed as sensor devices for measuring the mass of minute samples (see, for example, Patent Documents 1 to 6). In these QCM sensors, the mass of a sample is calculated from the change in vibration frequency when the sample is attached to the surface of a quartz oscillator that is vibrated by applying a voltage.

[0003] It has also been proposed that such QCM sensors can be used as detection devices that selectively detect only specific molecular structures, DNA, biomolecules, etc. by immobilizing host molecules on the surface of the quartz crystal oscillator and appropriately designing the substances that attach to the host molecules (see, for example, Non-Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2004-184256 [Patent Document 2] Japanese Patent Application Laid-Open No. 2005-274165 [Patent Document 3] Japanese Patent Application Laid-Open No. 2007-057291 [Patent Document 4] Japanese Patent Application Laid-Open No. 2007-192650 [Patent Document 5] Japanese Patent Application Laid-Open No. 2009-250808 [Patent Document 6] Japanese Patent Application Laid-Open No. 2014-139557 [Non-patent literature]

[0005] [Non-Patent Document 1] Hiroshi Yoshimine et al. “Small Mass-Change Detectable Quartz Crystal Microbalance and Its Application to Enzymatic One-Base Elongation on DNA”, October 4, 2011, Analytical Chemistry 2011, 83, 22, 8741-8747 Summary of the Invention [Problem to be solved by the invention]

[0006] As mentioned above, sensor devices using QCM sensors can selectively detect only specific molecular structures, DNA, biomolecules, etc., so it is desirable to be able to take the sensor device outdoors and easily detect viruses in samples or microscopic substances in gases.

[0007] However, conventional sensor devices using QCM sensors require a complex structure for supplying samples to the surface of the QCM sensor, limiting the miniaturization of the sensor device. Furthermore, to accurately measure even the slightest changes in the frequency of the quartz crystal oscillator, a large, high-performance frequency measurement device was required. Furthermore, to supply the power required to operate the frequency measurement device, a commercial power source or a large storage battery was required. This resulted in a large system for operating the sensor device, making it difficult to improve portability.

[0008] Therefore, the present invention has been made in consideration of the above-mentioned conventional problems, and aims to provide a sensor device and a frequency measurement method that can supply a sample to a quartz crystal oscillator with a simple structure and that can be made smaller and lighter. [Means for solving the problem]

[0009] In order to solve the above problem, the sensor device of the present invention comprises a quartz oscillator having electrodes formed on its front and back surfaces and vibrating when an AC voltage is applied, a housing for accommodating the quartz oscillator, and a terminal portion electrically connected to the electrodes and electrically connected to the outside of the housing, the housing having a mounting plate portion for mounting the quartz oscillator, a frame portion placed on the mounting plate portion, and a cover portion placed on the frame portion, the frame portion having a storage chamber for accommodating the quartz oscillator, and a sample inlet channel and a sample outlet channel which are grooves formed and communicated with the storage chamber, the cover portion having an inlet formed at a position corresponding to the sample inlet channel and an outlet formed at a position corresponding to the sample outlet channel.

[0010] In the sensor device of the present invention, the frame body is sandwiched between the mounting plate and the cover, and the quartz oscillator is placed in the storage chamber provided in the frame body. This allows the sample to be supplied into the storage chamber via the sample inlet and sample outlet paths, making it possible to supply the sample to the quartz oscillator with a simple structure and further reducing the size and weight. In one aspect of the present invention, the frame portion is made of a gel material.

[0011] In one aspect of the present invention, the cover portion has an access opening formed at a position corresponding to the storage chamber, and a detachable lid portion is provided to cover the access opening.

[0012] In one aspect of the present invention, the sample inlet channel is narrower and shorter than the sample outlet channel.

[0013] In one aspect of the present invention, a probe molecule is immobilized on the surface of the quartz crystal oscillator.

[0014] In addition, in order to solve the above problem, the sensor device of the present invention includes a quartz crystal oscillator having electrodes formed on its front and back surfaces and vibrating at a natural frequency f1 when a predetermined AC voltage is applied, terminal portions electrically connected to the electrodes, and a frequency measurement portion that applies the predetermined AC voltage to the electrodes via the terminal portions and measures an actual vibration frequency f2 of the quartz crystal oscillator, wherein the frequency measurement portion includes a reference oscillation portion that oscillates at a reference frequency f3, a first counter that measures the number of vibrations of the reference oscillation portion, and a second counter that measures the number of vibrations of the quartz crystal oscillator, and is characterized in that the vibration frequency f2 is calculated based on the period t until the second number of measurements c2 by the second counter reaches a specified number c3, the first number of measurements c1 by the first counter, and the reference frequency f3.

[0015] In the sensor device of the present invention, the number of vibrations of the quartz oscillator is measured by the second counter, and when the second counter measures the second measurement number c2, the actual vibration frequency f2 is calculated from the first measurement number c1, which is the number of vibrations of the reference oscillator, and the reference frequency f3.This makes it possible to measure accurate frequencies with a simple circuit configuration, and enables the device to be made smaller and lighter.

[0016] In one aspect of the present invention, the specified number of times c3 is obtained by subtracting the number of times Δc corresponding to the sample and liquid to be attached from the initial setting value.

[0017] In one aspect of the present invention, the first counter includes a first frequency divider circuit that divides and measures the number of oscillations of the reference oscillation unit.

[0018] In one aspect of the present invention, the second counter includes a second frequency divider circuit that divides and measures the number of oscillations of the crystal oscillator.

[0019] In one aspect of the present invention, the mass of the sample attached to the quartz crystal oscillator is calculated based on the natural frequency f1 and the vibration frequency f2.

[0020] In one aspect of the present invention, the output of the reference oscillator is shared as a clock signal that synchronizes the entire circuit.

[0021] In one aspect of the present invention, a probe molecule is immobilized on the surface of the quartz crystal oscillator.

[0022] In order to solve the above problem, the frequency measurement method of the present invention is characterized by comprising a voltage application step of applying a predetermined AC voltage to a quartz crystal resonator having a natural frequency f1, a reference oscillation step of oscillating a reference frequency f3 using a reference oscillation unit, a first measurement step of measuring the oscillation of the reference oscillation unit as a first measurement number c1, a second measurement step of measuring the oscillation of the quartz crystal resonator as a second measurement number c2, and a frequency calculation step of calculating an oscillation frequency f2 based on a period t until the second measurement number c2 reaches a specified number c3, the first measurement number c1, and the reference frequency f3.

[0023] In one aspect of the present invention, the specified number of times c3 is obtained by subtracting the number of times Δc corresponding to the sample and liquid to be attached from the initial setting value.

[0024] In one aspect of the present invention, a signal obtained by multiplying the output of the reference oscillator or an output signal of the first frequency divider circuit is distributed as a clock signal, thereby synchronizing the entire circuit. [Effects of the Invention]

[0025] The present invention can provide a sensor device and a frequency measurement method that can supply a sample to a quartz crystal oscillator with a simple structure and can be made smaller and lighter. [Brief explanation of the drawings]

[0026] [Figure 1] 1A and 1B are diagrams showing a sensor device 10 according to a first embodiment of the present invention, in which FIG. 1A is a schematic diagram showing the overall configuration of the sensor device, and FIG. 1B is a block diagram showing the configuration of a circuit portion. [Figure 2]2A and 2B are schematic diagrams illustrating the details of the quartz oscillator 15 used in the first embodiment, where FIG. 2A shows a quartz single crystal, FIG. 2B shows the cutting angle, and FIG. 2C shows the appearance of the quartz oscillator 15. [Figure 3] 2 is a block diagram showing an example of the configuration of a counter unit section 24. FIG. [Figure 4] 4A and 4B are schematic diagrams illustrating differences in operation regarding frequency measurement methods, where FIG. 4A shows Comparative Example 1, FIG. 4B shows Comparative Example 2, and FIG. 4C shows an example. [Figure 5] 5A and 5B are schematic diagrams showing the structure of the housing 14, where FIG. 5A is a schematic plan view, FIG. 5B is a schematic cross-sectional view at the AA position, FIG. 5C is a schematic exploded oblique view, and FIG. 5D is a partially enlarged plan view. [Figure 6] FIG. 1 is a schematic diagram showing a case where the sensor device 10 is used as a biosensor. [Figure 7] 7 is a graph showing the detection results of the biosensor shown in FIG. 6. [Figure 8] FIG. 1 is a process diagram illustrating in more detail the immobilization of probe molecules and the operation as a biosensor. [Figure 9] These are graphs showing the immobilization of probe molecules using existing equipment and its operation as a biosensor. Figure 9(a) shows modification with neutravidin, Figure 9(b) shows the immobilization of biotinylated DNA 52 as a probe molecule and the addition of a single biotin molecule that inhibits the immobilization reaction of the probe molecule, and Figure 9(c) shows the change in frequency due to the supply of complementary strand DNA and mismatched DNA. [Figure 10] FIG. 10 is a schematic diagram showing a case where an antigen is detected using an antibody as a probe molecule of a quartz crystal oscillator 15 in a sensor device 10 according to a second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0027] (First embodiment) Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. The same or equivalent components, members, and processes shown in each drawing will be assigned the same reference numerals, and redundant explanations will be omitted where appropriate. FIG. 1 shows a sensor device 10 according to this embodiment, with FIG. 1(a) being a schematic diagram showing the overall configuration of the sensor device, and FIG. 1(b) being a block diagram showing the configuration of the circuit portion. As shown in FIG. 1(a), the sensor device 10 includes a case 11, a battery 12, a circuit board 13, a housing 14, and a quartz crystal oscillator 15.

[0028] The case 11 is an outer shell that houses and holds the components of the sensor device 10, and has a substantially rectangular parallelepiped shape. There are no limitations on the material that can be used to form the case 11, and known resin materials, metal materials, ceramic materials, etc. The size and shape of the case 11 are also not limited, but it can be configured to be the same size as a transportation IC card, approximately 54 mm long and 86 mm wide.

[0029] The battery unit 12 is a power supply component that stores power and supplies it to the circuit board 13, and may be, for example, a primary battery such as an alkaline battery or a secondary battery such as a lithium ion battery. If necessary, the battery unit 12 may be provided with a charging circuit so that it can be charged by power supplied from an external power source.

[0030] Circuit board 13 is a component that mounts an electric circuit that operates using power from battery unit 12. There are no limitations on the specific structure of circuit board 13, and a conventionally known printed wiring board or the like can be used. A connector unit (not shown) is mounted on a part of circuit board 13, and crystal unit 15 in housing 14 and the electric circuit on circuit board 13 can be electrically connected via the connector unit.

[0031] The housing 14 is a member that houses the quartz oscillator 15 therein and ensures electrical connection between the circuit board 13 and the quartz oscillator 15. The housing 14 also has a flow path formed therein that supplies gas or liquid containing a sample to be detected to the quartz oscillator 15. The detailed structure of the housing 14 will be described later.

[0032] The quartz crystal unit 15 is an electronic component made by cutting out a single crystal of quartz and forming electrodes on its front and back surfaces. When a predetermined AC voltage is applied to the electrodes on both surfaces, the quartz crystal unit 15 oscillates at a natural frequency due to the piezoelectric effect. The electrodes on both surfaces of the quartz crystal unit 15 are electrically connected to the connector of the circuit board 13 via terminals, and the quartz crystal unit 15 oscillates with the AC voltage supplied from the circuit board 13, transmitting voltage fluctuations according to the oscillation frequency to the circuit board 13. Here, the natural frequency of the quartz crystal unit 15 is the frequency at which the quartz crystal unit 15 oscillates when a predetermined AC voltage is applied with electrodes formed on its front and back surfaces.

[0033] An electric circuit for oscillating crystal resonator 15 and measuring its frequency is configured on circuit board 13. As shown in Fig. 1(b), the electric circuit on circuit board 13 includes regulator 21, temperature compensated crystal oscillator 22, information processing section 23, counter unit section 24, inverting amplifier inverter section 25, waveform conversion inverter section 25', and wireless communication section 26. The combination of regulator 21, temperature compensated crystal oscillator 22, information processing section 23, counter unit section 24, inverting amplifier inverter section 25, and waveform conversion inverter section 25' configures the frequency measurement section of the present invention.

[0034] The regulator 21 is a part for controlling the voltage value of the power supplied from the battery unit 12 to a constant value. The specific configuration of the regulator 21 is not limited, and a conventionally known linear regulator or switching regulator can be used. The power converted to a predetermined voltage value by the regulator 21 is supplied to each part on the circuit board 13.

[0035] The temperature-compensated crystal oscillator 22 is a component that oscillates at a reference frequency using a quartz single crystal separate from the crystal resonator 15. The temperature-compensated crystal oscillator 22 is also equipped with a temperature compensation function, allowing it to continue oscillating at a stable reference frequency regardless of changes in the ambient temperature, even when the ambient temperature is in the range of -40 to +85°C. A conventionally known method can be used to realize the temperature compensation function. The oscillation frequency of the temperature-compensated crystal oscillator 22 corresponds to the reference frequency in the present invention, and an example of this frequency is 32 MHz. Since the temperature-compensated crystal oscillator 22 oscillates at the reference frequency, it corresponds to the reference oscillation unit in the present invention. While the temperature-compensated crystal oscillator 22 is provided separately from the counter unit 24 in this example, the temperature-compensated crystal oscillator 22 may be included within the counter unit 24, as described below.

[0036] The temperature-compensated crystal oscillator 22 is also the source of a clock signal for synchronizing the entire circuit. The output of the temperature-compensated crystal oscillator 22 is multiplied or divided and distributed as a clock signal to the information processing section 23 and counter unit section 24, which will be described later. The entire circuit, including the information processing section 23 and counter unit section 24, can be operated in synchronization based on the stable clock signal output by the temperature-compensated crystal oscillator 22.

[0037] The information processing unit 23 is an arithmetic unit that processes information according to a predetermined program and controls each part of the electronic circuit on the circuit board 13, and is realized by a CPU (Central Processing Unit) or the like. The information processing unit 23 also acquires information from each part of the electronic circuit on the circuit board 13 and performs arithmetic processing according to the program. A memory device, an input / output device, a display device, etc. may be connected to the information processing unit 23, and it may record programs and data, output and display arithmetic results, etc.

[0038] The counter unit 24 is a part that measures the number of vibrations of the crystal oscillator 15 when an AC voltage is applied to the crystal oscillator 15 to cause it to oscillate. Information on the number of vibrations of the crystal oscillator 15 measured by the counter unit 24 is transmitted to the information processing unit 23.

[0039] The inverting amplifier inverter section 25 inverts and amplifies the sine wave vibration generated by the oscillation of the crystal unit 15, and the waveform conversion inverter section 25' converts the amplified sine wave voltage fluctuation into a square wave. By converting the sine wave vibration into a square wave by the waveform conversion inverter section 25', the counter unit section 24 counts the number of oscillations of the crystal unit 15 as digital information. Here, an example is shown in which two inverting amplifier inverter sections 25 and a waveform conversion inverter section 25' are provided separately from the counter unit section 24, but as will be described later, two inverting amplifier inverter sections 25 and a waveform conversion inverter section 25' may also be included within the counter unit section 24.

[0040] The wireless communication unit 26 is a part that communicates information between a device provided outside the sensor device 10 and the information processing unit 23. The specific configuration and specifications of the wireless communication unit 26 are not limited, and known technologies such as infrared communication, communication using a mobile phone network, and short-range wireless communication can be used.

[0041] 1(a) and 1(b), the sensor device 10 of this embodiment accommodates a battery unit 12, a circuit board 13, a housing 14, and a quartz oscillator 15 in a case unit 11, and is capable of communicating with the outside via a wireless communication unit 26. Therefore, the sensor device 10 can be operated using only the power stored in the battery unit 12 without the need for a separate power supply, and the obtained measurement results can be collected via the wireless communication unit 26.

[0042] FIG. 2 is a schematic diagram illustrating the details of the quartz crystal resonator 15 used in this embodiment. FIG. 2(a) shows a quartz single crystal, FIG. 2(b) shows the cutting angle, and FIG. 2(c) shows the appearance of the quartz crystal resonator 15. As shown in FIGS. 2(a) and 2(b), the quartz crystal resonator 15 is cut in an AT-cut manner, in which the xz plane is rotated around the x-axis and tilted at an angle of θ degrees with respect to the r-plane of the quartz single crystal. A typical tilt angle θ used in AT-cut crystals is 2° 58'. In this embodiment, the crystal is cut from a tilt angle θ within the range of 2° 59' 30' ±15'. At this tilt angle θ, the frequency change rate of the quartz crystal resonator 15 due to temperature changes around 25°C is small, allowing for a constant frequency to be obtained around room temperature. Electrodes 15a and 15b are formed on the front and back surfaces of the cut quartz crystal resonator 15, respectively.

[0043] Fig. 3 is a block diagram showing an example of the configuration of the counter unit section 24. As shown in Fig. 3, the counter unit section 24 is connected to an oscillation circuit 31 and a temperature compensated crystal oscillator 36, and includes a frequency divider circuit 32, a crystal oscillation counter 33, a comparator 34, a register 35, a frequency divider circuit 37, a reference oscillation counter 38, and a register 39.

[0044] The oscillator circuit 31 applies a predetermined AC voltage to the crystal oscillator 15 to oscillate the crystal oscillator 15, and transmits the voltage fluctuations generated by the oscillation of the crystal oscillator 15 to the frequency divider circuit 32. The oscillator circuit 31 includes the inverting amplifier inverter unit 25 and the waveform conversion inverter unit 25' shown in FIG. 1. The specific configuration of the oscillator circuit 31 is not limited, and any known circuit configuration for oscillating the crystal oscillator 15 can be used. The specific oscillation frequency of the oscillator circuit 31 is not limited, but as an example, a frequency of 27 MHz or higher can be used when detecting DNA. Furthermore, a frequency of 9 MHz or higher can be used when detecting proteins, etc.

[0045] The frequency divider circuit 32 divides the voltage fluctuation caused by the oscillation of the crystal oscillator 15 transmitted from the oscillator circuit 31 and transmits the divided voltage to the crystal oscillation counter 33. An example of the frequency divider circuit 32 is a 1 / 8 frequency divider, which outputs one high signal corresponding to four pulse periods from the oscillator circuit 31 and one low signal corresponding to the following four pulse periods. By providing the frequency divider circuit 32 between the oscillator circuit 31 and the crystal oscillation counter 33, components with a small number of bits and operating at a low frequency can be used for the crystal oscillation counter 33, thereby achieving miniaturization and power saving. The frequency divider circuit 32 corresponds to the second frequency divider circuit in this invention.

[0046] The crystal counter 33 is a part that counts the number of rising or falling edges of the voltage fluctuation output from the frequency divider circuit 32, and corresponds to the second counter in the present invention. The count count output measured by the crystal counter 33 is compared with the value recorded in the register 35 by the comparator 34, as will be described later. When a match output is output from the comparator 34 to the crystal counter 33, the count is reset and measurement is restarted.

[0047] The comparator 34 compares the output of the number of measurements measured by the crystal vibration counter 33 with the value of the specified number of times recorded in the register 35, and if the two values ​​match, outputs a match output to the crystal vibration counter 33, the reference vibration counter 38, and the register 39. This output triggers the transfer of data from the reference vibration counter 38 to the register 39.

[0048] Register 35 is a memory unit that records the value of a specified number of times to be compared with the number of measurements made by crystal vibration counter 33. The recorded specified number of times is the value obtained by dividing the natural frequency of crystal oscillator 15 by frequency divider circuit 32. For example, when the natural frequency is 27 MHz and the division ratio is r1=1 / 8, the recorded specified number of times is 3,375,000 times.

[0049] The temperature-compensated crystal oscillator 36 is equipped with a temperature compensation function and oscillates at a reference frequency regardless of temperature. The oscillation frequency of the temperature-compensated crystal oscillator 36 corresponds to the reference frequency in the present invention, and as an example, 32 MHz can be used. Since the temperature-compensated crystal oscillator 36 oscillates at the reference frequency, it corresponds to the reference oscillation unit in the present invention.

[0050] The frequency divider circuit 37 divides the voltage fluctuation due to the reference frequency transmitted from the temperature compensated crystal oscillator 36 and transmits the result to the reference vibration counter 38. An example of the frequency divider circuit 37 is a frequency divider with r2=1 / 2, which outputs one high signal corresponding to one pulse period from the temperature compensated crystal oscillator 36 and one low signal corresponding to the following pulse period. By providing the frequency divider circuit 37 between the temperature compensated crystal oscillator 36 and the reference vibration counter 38, components with a small number of bits and operating at a low frequency can be used as the reference vibration counter 38, thereby achieving miniaturization and power saving. The frequency divider circuit 37 corresponds to the first frequency divider circuit in this invention.

[0051] The reference vibration counter 38 is a part that measures the number of rising or falling edges of the voltage fluctuation output from the frequency divider circuit 37, and corresponds to the first counter in the present invention. The reference vibration counter 38 continues counting until a coincidence output is output from the comparator 34. When a coincidence output is output from the comparator 34, the number of measurements at that time is saved in the register 39, and the count is reset to restart measurement.

[0052] The register 39 is a memory unit that records the number of measurements when a coincidence output is output from the comparator 34 to the reference vibration counter 38. The number of measurements of the reference vibration counter 38 recorded in the register 39 is read by the information processing unit 23 and used to calculate the number of vibrations per unit time of the crystal oscillator 15 (actual vibration frequency).

[0053] Next, we will explain how to calculate the actual oscillation frequency of crystal oscillator 15. First, in the voltage application step, a predetermined AC voltage is applied to crystal oscillator 15 with natural frequency f1 to oscillate crystal oscillator 15. At this time, the voltage fluctuations caused by the oscillation of crystal oscillator 15 are converted into a square wave by oscillation circuit 31 and transmitted to frequency divider circuit 32, where they are converted at a predetermined frequency division ratio and transmitted to crystal oscillation counter 33.

[0054] In parallel with the voltage application process, a reference frequency f3 is oscillated by the temperature compensated crystal oscillator 36 in a reference oscillation process. At this time, the voltage fluctuation caused by the oscillation of the temperature compensated crystal oscillator 36 is transmitted to the frequency divider circuit 37, converted at a predetermined frequency division ratio, and transmitted to the reference oscillation counter 38. This voltage application process and reference oscillation process are executed continuously during the measurement period.

[0055] Next, the reference vibration counter 38 starts counting in synchronization with the start timing of the crystal vibration counter 33. Measuring the first number of measurements c1 by the reference vibration counter 38 corresponds to the first measurement step in the present invention, and measuring the second number of measurements c2 by the crystal vibration counter 33 corresponds to the second measurement step in the present invention. The first measurement step and the second measurement step are repeated until the second number of measurements c2 becomes equal to the specified number of times c3.

[0056] When the second measurement count c2 measured by the crystal vibration counter 33 becomes equal to the specified count c3 recorded in the register 35, the comparator 34 outputs a match signal, and the first measurement count c1 at that time is recorded in the register 39. In addition, the measurement counts of the reference vibration counter 38 and the crystal vibration counter 33 are reset.

[0057] Next, in the frequency calculation step, the information processing unit 23 calculates the actual oscillation frequency f2 of the crystal unit 15 based on the second measurement count c2, the first measurement count c1 recorded in the register 39, and the reference frequency f3 of the temperature compensated crystal oscillator 36. More specifically, in the first step, the time t required for the crystal counter 33 to count the second measurement count c2 is calculated as t = c1 / (r2 × f3) using the reference frequency f3, the first measurement count c1, and the frequency division ratio r2. Next, in the second step, the actual oscillation frequency f2 is calculated as f2 = c2 / (r1 × t).

[0058] That is, the reference vibration counter 38 counts the first measurement number c1 for the period of time t during which the second measurement number c2, which is the measurement number obtained by dividing the frequency of the crystal oscillator 15, reaches the specified number c3, thereby calculating the time t from the frequency of the temperature compensated crystal oscillator 36. This makes it possible to calculate the accurate time and frequency even when measuring the frequency of the crystal oscillator 15 and the temperature compensated crystal oscillator 36 via the frequency divider circuit 32 and the frequency divider circuit 37. Furthermore, by using the frequency divider circuit 32 and the frequency divider circuit 37, it is possible to use low-power reference vibration counter 38 and crystal vibration counter 33 that have a small number of bits and operate at a low frequency, thereby achieving power savings.

[0059] In actual measurements, the vibration frequency f2 of the quartz crystal oscillator 15 decreases when the quartz crystal oscillator 15 comes into contact with a sample or liquid, resulting in a longer time until the second measurement count c2 equals the specified count c3. In measurements where the vibration frequency f2 is measured repeatedly at predetermined intervals, the specified count c3 can be set by subtracting the count Δc corresponding to the decrease in the vibration frequency f2 from the initial setting so that the time t does not exceed the predetermined time. Here, the initial setting value of the specified count c3 is the number determined by the vibration frequency f2 of the quartz crystal oscillator 15 over a predetermined time (for example, one second) when no fluid such as a liquid or sample is attached to the quartz crystal oscillator 15.

[0060] The number of times Δc to be subtracted based on contact with a fluid such as a liquid and adhesion of a sample can be determined using the previously published Kanazawa equation (see, for example, K. Keiji Kanazawa et al., "Frequency of a Quartz Microbalance in Contact with Liquid," October 29, 1984, Analytical Chemistry 1985, 57, 1771-1772) and Saurbrey equation (see, for example, Gunter Sauerbrey, "Verwendung von Schwingquarzen zur Wagung dunner Schichten und zur Mikrowagung," April 1959, Zeitschrift fur Physik, 1959, 155, 206-222). For example, when the natural frequency of the quartz crystal unit 15 is 27 MHz, Δc corresponding to contact with a fluid such as a liquid and adhesion of a sample can be calculated as 1250 times, which is 1 / 8 of 10,000 times.

[0061] Furthermore, the information processing unit 23 or the external computing device calculates the mass of the sample attached to the quartz crystal oscillator 15 in a mass calculation step from the actual vibration frequency f2 of the quartz crystal oscillator 15 calculated in the vibration frequency calculation step. There are no specific limitations on the method for calculating the mass, and various methods used in conventional QCM sensors can be used. In this case, it is preferable to calculate the mass by referring to the mass of the probe molecules immobilized on the surface of the quartz crystal oscillator 15, the mass of the target molecules bound to the probe molecules, changes in the load frequency due to the influence of the fluid (gas or liquid) containing the sample supplied to the quartz crystal oscillator 15, etc.

[0062] FIG. 4 is a schematic diagram illustrating differences in operation regarding frequency measurement methods, with FIG. 4(a) showing Comparative Example 1, FIG. 4(b) showing Comparative Example 2, and FIG. 4(c) showing an embodiment. The block diagram shown in the middle of the figure shows the circuit configuration in each example. The timing chart shown in the bottom of the figure schematically shows measurement by the crystal vibration counter 33. The timing chart shown in the top of the figure schematically shows measurement by the reference vibration counter 38. In each example, the temperature-compensated crystal oscillator 36 oscillates at a reference frequency of 32 MHz, the division ratio of the frequency divider circuit 37 is r2=1 / 2, and the natural frequency of the crystal resonator 15 is 27 MHz.

[0063] In Comparative Example 1 shown in FIG. 4(a), the oscillation frequency of the temperature-compensated crystal oscillator 36 is used as a timer, and no divider circuit is interposed between the oscillator circuit 31 and the crystal oscillation counter 33. In this case, one second is calculated when the oscillation frequency of the temperature-compensated crystal oscillator 36 reaches 32 million oscillations, i.e., when the reference oscillation counter 38 measures 16 million oscillations from the frequency divider circuit 37. During this one second, the crystal oscillation counter 33 measures the oscillations of the crystal unit 15 to calculate the actual oscillation frequency f2. However, to measure an oscillation frequency of approximately 27 MHz, the crystal oscillation counter 33 must have 25 bits or more, which allows it to measure 27 million oscillations or more, and it must be driven at a high frequency of 27 MHz or more. This requires a high-performance counter device, which results in high power consumption. Furthermore, even when a high-performance counter device is used as the crystal oscillation counter 33, an error E1 inevitably occurs only during the last oscillation of one second, which is less than one oscillation.

[0064] In Comparative Example 2 shown in Figure 4(b), the frequency of the temperature-compensated crystal oscillator 36 is used as a timer, and a frequency divider circuit 32 is inserted between the oscillator circuit 31 and the crystal vibration counter 33. The frequency division ratio of the frequency divider circuit 32 is r1 = 1 / 8. In this case, one second is calculated when the temperature-compensated crystal oscillator 36 reaches 32 million oscillations, i.e., when the reference oscillation counter 38 measures 16 million oscillations from the frequency divider circuit 32. The number of oscillations measured by the crystal vibration counter 33 during this one second is approximately 3.375 MHz, which is 1 / 8 of approximately 27 MHz. Therefore, a 22-bit count and a low frequency drive of approximately 4 MHz for the crystal vibration counter 33 are sufficient, thereby reducing the power consumption of the counter device. However, an error E2 occurs, corresponding to the last oscillation less than one in one second, and the error becomes larger as the frequency is divided by 1 / 8.

[0065] In the embodiment shown in Figure 4(c), the frequency of the crystal oscillator 15 is used as a timer, and a frequency divider circuit 32 is interposed between the oscillator circuit 31 and the crystal oscillator counter 33. The frequency divider circuit 32 has a frequency division ratio of r1 = 1 / 8. Because the frequency divider circuit 32 is used, the crystal oscillator counter 33 can be driven at a low frequency of approximately 22 bits and 4 MHz, thereby reducing the power consumption of the counter device. In this case, the crystal oscillator counter 33 measures the output from the frequency divider circuit 32, and the time when it reaches a specified frequency c3 is defined as t. If the specified frequency c3 is set to 3,375,000, which is 1 / 8 of 27 MHz, multiplying this specified frequency c3 by 8 is the natural frequency f1 of the crystal oscillator 15, so the time t is approximately 1 second. Here, the frequency divider circuit 32 is used to count the frequency, but the time is not measured exactly every second. Rather, the time t is determined based on the frequency of the oscillations, so oscillations less than one are not included, allowing for accurate measurement of the frequency of the oscillations.

[0066] At the same time, during the time t during which the specified number of times c3 is accurately measured, the reference vibration counter 38 measures the output of the frequency divider circuit 37 as the first measurement number c1, and the time t can be calculated from the reference frequency f3 and the first measurement number c1. Specifically, c1 / r2 is approximately 32 million times, which is then divided by the reference frequency f3, 32 MHz. At this time, an error E3 occurs due to the last vibration less than one time during the time t, but by making c1 >> c2, the error in the time t becomes extremely small. Therefore, by using the frequency divider circuit 32 and the frequency divider circuit 37, it is possible to accurately calculate the time t and accurately calculate the actual vibration frequency f2 of the crystal oscillator 15 while reducing the power consumption of the crystal vibration counter 33 and the reference vibration counter 38.

[0067] In the sensor device 10 of the embodiment, a lithium-ion battery with a voltage of 3.8 V and a capacity of 60 mAh was used as the battery section 12, and measurements were continued with the inside of the flow path of the casing 14 filled with water, resulting in an operating time of approximately 4 hours.

[0068] Next, the structure of the housing 14 that houses the crystal oscillator 15 will be described in detail. Fig. 5 is a schematic diagram showing the structure of the housing 14, with Fig. 5(a) being a schematic plan view, Fig. 5(b) being a schematic cross-sectional view taken along the line AA, Fig. 5(c) being a schematic exploded perspective view, and Fig. 5(d) being a partially enlarged plan view. As shown in Fig. 5, the housing 14 of the sensor device 10 includes a back film 41, a mounting plate portion 42, a frame portion 43, a cover portion 44, and a lid portion 45.

[0069] The back surface film 41 is a film-like member attached to the back surface of the mounting plate portion 42 to protect the mounting plate portion 42. There are no restrictions on the material that can be used for the back surface film 41, and a resin film, a metal film, or the like can be used as needed. Here, an example is shown in which the back surface film 41 is prepared separately from the mounting plate portion 42, but if the durability of the mounting plate portion 42 can be sufficiently ensured, the back surface film 41 may be omitted.

[0070] The mounting plate 42 is a generally plate-shaped member on whose surface the crystal unit 15 and frame 43 are mounted, and on whose back surface a back film 41 is attached. A wiring layer electrically connected to the electrodes 15a and 15b of the crystal unit 15 is formed, and terminals 42a are provided at the ends of the wiring layer. The mounting plate 42 may be made of any material, including glass epoxy resin used in printed wiring boards, liquid crystal polymer materials for printed circuit boards, paper phenolic resin, paper epoxy resin, aluminum and its alloys, ceramics, and polyimide resin. When the frame 43 is made of a gel material, as described below, polyimide resin is preferably used for the mounting plate 42. The terminals 42a electrically connect the housing 14 to the circuit board 13 and are shaped to mate with connectors 42b mounted on the circuit board 13.

[0071] The frame 43 is a frame-shaped member placed on the mounting plate 42 and has a space formed therein for accommodating the quartz crystal oscillator 15. The frame 43 includes a storage chamber 43a, a sample inlet channel 43b, and a sample outlet channel 43c. The quartz crystal oscillator 15 is accommodated in the storage chamber 43a. The frame 43 may be made of any material, including insulating materials such as resins and ceramics. However, it is preferable to make the frame 43 from a gel-like material and attach it to the surface of the mounting plate 42. Using a gel-like material for the frame 43 improves adhesion between the mounting plate 42 and the cover 44, effectively preventing leakage of the fluid to be detected. Furthermore, the flexibility of the gel-like material reduces pressure when injecting the fluid to be detected. In this embodiment, the frame 43 is made of a gel-like material and the components are directly attached to each other. However, an adhesive or glue layer may be interposed between the components.

[0072] The storage chamber 43a is a substantially circular through-hole provided in the frame portion 43, and is accommodated so that the surface of the quartz oscillator 15 is positioned at the center. A sample inlet channel 43b and a sample outlet channel 43c extend from a portion of the outer periphery of the storage chamber 43a. As will be described later, the storage chamber 43a is filled with a fluid (liquid or gas) that is the detection target, and forms a space in which the detection target contained in the fluid adheres to the probe molecules immobilized on the quartz oscillator 15.

[0073] The sample inlet channel 43b is a groove formed in communication with the storage chamber 43a from a position directly below an inlet 44b (described later) and is a path for introducing the fluid to be detected into the storage chamber 43a. The sample outlet channel 43c is a groove formed in communication with the storage chamber 43a from a position directly below an outlet 44c (described later) and is a path for discharging the fluid to be detected from the storage chamber 43a to the outside.

[0074] As shown in Figures 5(a) and 5(d), the sample inlet channel 43b is narrower than the sample outlet channel 43c and shorter in length. This allows the liquid to be detected, supplied from the sample inlet channel 43b, to quickly reach the storage chamber 43a and be easily discharged from the storage chamber 43a to the outside via the sample outlet channel 43c. Furthermore, when the fluid to be detected is a liquid, the liquid is drawn toward the sample inlet channel 43b rather than the sample outlet channel 43c due to surface tension, preventing the inclusion of air bubbles. Furthermore, because the cross-sectional area of ​​the sample inlet channel 43b is smaller than that of the sample outlet channel 43c, evaporation of the liquid is suppressed, preventing an increase in the concentration of the detection target in the storage chamber 43a.

[0075] The cover 44 is a film-like member placed on the frame 43. As shown in FIGS. 5(a) to 5(d), the cover 44 has an access opening 44a, an inlet 44b, and an outlet 44c. The material for the cover 44 is not limited, and a resin film, a metal film, or the like can be used. When the frame 43 is made of a gel-like material, a polyimide film is preferably used to improve adhesion to the frame 43. The access opening 44a is an opening formed at a position corresponding to the storage chamber 43a. The access opening 44a is formed in substantially the same shape as the storage chamber 43a, so that when the cover 44 is attached to the frame 43, the interior of the storage chamber 43a is exposed above the cover 44. The inlet 44b is an opening formed at a position corresponding to the end of the sample inlet 43b. The outlet 44c is an opening formed at a position corresponding to the end of the sample outlet 43c.

[0076] The lid 45 is a plate-like member that covers the working opening 44a and is detachably disposed on the cover 44. The configuration of the lid 45 is not limited, but a structure in which an adhesive gel-like material is attached to the underside of a film-like member is preferable. When the lid 45 is attached to the cover 44, the working opening 44a is covered, keeping the space within the storage chamber 43a airtight or liquid-tight, preventing leakage of the fluid to be detected from the inside. When the lid 45 is removed from the cover 44, the working opening 44a is opened, allowing an operator to access the interior space of the storage chamber 43a. With the working opening 44a open, the surface of the quartz crystal oscillator 15 is also accessible from the outside, allowing for tasks such as removing probe molecules immobilized on the surface or immobilizing new probe molecules on the surface. Therefore, the structure in which the working opening 44a is covered with the detachable lid 45 facilitates changes in the use of the sensor device 10 and maintenance work.

[0077] The housing 14 shown in FIG. 5 is connected to the circuit board 13, and the fluid to be detected is injected into the storage chamber 43a while the quartz oscillator 15 is oscillating. Specifically, a liquid containing a sample is injected through the inlet 44b using a micropipette or the like. The injected liquid flows from the inlet 44b through the sample inlet 43b and fills the storage chamber 43a. After the storage chamber 43a is filled, the liquid is discharged to the outside through the sample outlet 43c and the outlet 44c. If the sample contained in the liquid that has filled and accumulated in the storage chamber 43a adheres to the probe molecules, the mass of the quartz oscillator 15 changes, causing a change in the oscillation frequency f2. Therefore, the presence or absence and mass of the target can be detected based on the change in the oscillation frequency f2.

[0078] FIG. 6 is a schematic diagram showing a case where the sensor device 10 is used as a biosensor. As shown in FIG. 6(a), electrodes 15a and 15b are formed on the front and back surfaces of the quartz crystal oscillator 15 of the sensor device 10. As shown in FIG. 6(b), neutravidin 51 is immobilized on the front electrode 15a, and one strand of biotinylated DNA 52 modified with biotin 52a is immobilized to the neutravidin 51. As shown in FIG. 6(c), even if DNA 54, whose base sequence has been partially modified to have a sequence that is not complementary to the biotinylated DNA 52, is introduced into the storage chamber 43a, the biotinylated DNA 52 and DNA 54 do not form a double strand, and the mass of the quartz crystal oscillator 15 does not change, so the vibration frequency f2 does not change either. On the other hand, as shown in Figure 6(d), when target DNA 55, which has a complementary sequence to biotinylated DNA 52, is introduced into storage chamber 43a, biotinylated DNA 52 and DNA 55 form a double strand, causing a change in the mass of quartz oscillator 15 and a change in vibration frequency f2.

[0079] Figure 7 is a graph showing the detection results of the biosensor shown in Figure 6. The horizontal axis represents the elapsed time since the liquid containing the sample was injected into the storage chamber 43a, and the vertical axis represents the change in the frequency of the quartz oscillator 15. In Figure 7, the solid line represents the time since the target DNA 55 was introduced, and the dashed line represents the time since the DNA 54 with one base displacement was introduced. The liquid was introduced at the time indicated by the arrow in the graph, and during the injection operation, temporary changes in the frequency occurred due to the flow and pressure of the liquid within the storage chamber 43a.

[0080] As shown in Figure 7, the DNA 54 with one base displacement shows a small change in frequency after the liquid is injected. In contrast, the target DNA 55 shows a continuous change in frequency immediately after the liquid is injected, and it can be confirmed that the double strand of the probe immobilized on the neutravidin 51 and the biotinylated DNA 52 increases over time, and the mass of the quartz crystal oscillator 15 gradually increases. Therefore, by using the sensor device 10 of this embodiment, the target DNA 55 can be selectively detected with high accuracy.

[0081] Figure 8 is a process diagram that further explains the immobilization of probe molecules and their operation as a biosensor. First, 3,3-dithiodipropionic acid is applied to the surface of electrode 15a of quartz crystal oscillator 15 to introduce carboxyl groups. Next, N-hydroxysuccinimide (NNHS) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) are applied to the carboxyl groups to form activated esters on the surface of electrode 15a. Next, neutravidin is applied to immobilize the neutravidin. Next, biotinylated DNA 52 is bound to the neutravidin to immobilize the probe molecules. When complementary DNA is supplied as a sample, it forms a double strand with the DNA of the probe molecule, changing the frequency of the quartz crystal oscillator 15. On the other hand, when mismatched DNA, which is not complementary but has a partially modified base sequence, is supplied as a sample, it does not form a double strand with the DNA of the probe molecule, and the frequency of the quartz crystal oscillator 15 does not change.

[0082] Figure 9 is a graph showing the immobilization of probe molecules using existing equipment and its operation as a biosensor. Figure 9(a) shows modification with neutravidin, Figure 9(b) shows the immobilization of biotinylated DNA and the addition of a single biotin molecule to inhibit the immobilization reaction of biotinylated DNA 52 in order to adjust the amount of immobilization. Figure 9(c) shows the change in frequency due to the supply of complementary DNA and mismatched DNA. As shown in Figure 9(a), when 3 μl of a solution containing neutravidin at a concentration of 10 mg / ml is injected into the biosensor chamber, neutravidin is immediately immobilized on the surface of the quartz crystal oscillator 15, causing a change in the frequency of the quartz crystal oscillator 15. It can be seen that a sufficient amount of neutravidin has been immobilized after 30 to 40 minutes.

[0083] 9(b), when 2.5 μl of 10 μM biotinylated DNA 52 is injected into the biosensor chamber, the neutravidin 51 and biotinylated DNA 52 bind, causing a change in vibration frequency. Then, when 1 μl of 1 mM biotin molecules is injected into the biosensor chamber, biotin 52a binds to the biotin-binding site of neutravidin 51, inhibiting the binding of biotinylated DNA 52. This stops the change in vibration frequency, allowing the amount of immobilized biotinylated DNA 52 to be adjusted.

[0084] Next, as shown in Figure 9(c), 2.5 μl, 2.5 μl, 5 μl, and 5 μl of 10 μM complementary DNA 55 and mismatch DNA 54 were injected into the biosensor chamber over time. As shown by the solid line in Figure 9(c), when mismatch DNA 54 was injected, it did not form a double strand with the probe DNA, and the oscillation frequency remained almost unchanged. In contrast, as shown by the dashed line, when complementary DNA 55 was injected, the oscillation frequency changed up to the third injection, but even after injecting more than the predetermined amount, the oscillation frequency remained unchanged. This is because, even if an excess amount of complementary DNA 55 was supplied compared to the amount of biotinylated DNA 52 bound to neutravidin 51, the complementary DNA 55 was not captured by the double strand, and the mass on the quartz crystal oscillator 15 did not change.

[0085] As described above, in the sensor device 10 of the present invention, the frame body portion 43 is sandwiched between the mounting plate portion 42 and the cover portion 44, and the quartz oscillator 15 is placed in the storage chamber 43a provided in the frame body portion 43, so that the sample can be supplied into the storage chamber 43a via the sample inlet path 43b and the sample outlet path 43c. This makes it possible to supply the sample to the quartz oscillator 15 with a simple structure, and further enables the device to be made smaller and lighter.

[0086] In addition, the number of vibrations of the crystal oscillator 15 is measured by the crystal vibration counter 33, and when the crystal vibration counter 33 measures the second measurement number c2, the actual vibration frequency f2 is calculated from the first measurement number c1, which is the number of vibrations of the temperature-compensated crystal oscillator 36, and the reference frequency f3, so that an accurate frequency can be measured with a simple circuit configuration, making it possible to reduce the size and weight.

[0087] (Second embodiment) Next, a second embodiment of the sensor device of the present invention will be described with reference to FIG. 10. Descriptions overlapping with those of the first embodiment will be omitted. FIG. 10 is a schematic diagram illustrating a case in which an antigen is detected using an antibody as a probe molecule of the quartz oscillator 15 in the sensor device 10 of this embodiment. As shown in FIG. 10, in this embodiment, an antibody 61 is immobilized as a probe molecule on the electrode 15a of the quartz oscillator 15. When a liquid containing an antigen 62 is injected into the storage chamber 43a, the antigen 62 binds to the antibody 61, which is a probe molecule, increasing the mass of the quartz oscillator 15 and changing its vibration frequency. Therefore, in this embodiment, antigen testing can be easily performed using the sensor device 10.

[0088] The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope of the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention. [Explanation of symbols]

[0089] 10...Sensor device 11...Case part 12...Battery section 13...Circuit board 14...Housing 15...Crystal resonator 15a,15b...electrode 21...Regulator 22,36...Temperature compensated crystal oscillator 23...Information processing section 24...Counter unit 25...Inverting amplifier inverter section 25'...Waveform conversion inverter section 26...Radio communication section 31...Oscillator circuit 32...Frequency divider circuit 33...Crystal vibration counter 34...Comparator 35,39...Registers 37...Frequency divider circuit 38...Reference vibration counter 41...Back film 42...Placement plate section 42a...Terminal section 42b...Connector part 43...Frame body part 43a…Containment room 43b...Sample inlet channel 43c...Sample outflow channel 44...Cover part 44a...Work opening 44b…Inlet 44c…Discharge port 45...Lid part 51...Neutravidin 52...Biotinylated DNA 52a…Biotin 54,55…DNA 61…Antibody 62...antigen

Claims

1. A quartz crystal unit with electrodes formed on the front and back surfaces and vibrating when an AC voltage is applied; a housing that houses the crystal unit; a terminal portion electrically connected to the electrode and electrically connected to the outside of the housing; the housing has a mounting plate portion on which the crystal unit is mounted, a frame portion mounted on the mounting plate portion, and a cover portion mounted on the frame portion, a storage chamber for storing the quartz crystal oscillator, and a sample inlet channel and a sample outlet channel, which are grooves formed in communication with the storage chamber, are formed in the frame portion; the cover portion is formed with an inlet formed at a position corresponding to the sample inlet channel and an outlet formed at a position corresponding to the sample outlet channel, The sensor device is characterized in that the frame portion is made of a gel-like material.

2. A quartz crystal unit having electrodes formed on its front and back surfaces and vibrating when an AC voltage is applied; a housing that houses the crystal unit; a terminal portion electrically connected to the electrode and electrically connected to the outside of the housing; the housing has a mounting plate portion on which the crystal unit is mounted, a frame portion mounted on the mounting plate portion, and a cover portion mounted on the frame portion, a storage chamber for storing the quartz crystal oscillator, and a sample inlet channel and a sample outlet channel, which are grooves formed in communication with the storage chamber, are formed in the frame portion; the cover portion is formed with an inlet formed at a position corresponding to the sample inlet channel and an outlet formed at a position corresponding to the sample outlet channel, A sensor device characterized in that the cover portion has an access opening formed at a position corresponding to the storage chamber, and a removable lid portion is provided to cover the access opening.

3. A quartz crystal oscillator having electrodes formed on its front and back surfaces and vibrating when an AC voltage is applied; a housing that houses the crystal unit; a terminal portion electrically connected to the electrode and electrically connected to the outside of the housing; the housing has a mounting plate portion on which the crystal unit is mounted, a frame portion mounted on the mounting plate portion, and a cover portion mounted on the frame portion, a storage chamber for storing the quartz crystal oscillator, and a sample inlet channel and a sample outlet channel, which are grooves formed in communication with the storage chamber, are formed in the frame portion; the cover portion is formed with an inlet formed at a position corresponding to the sample inlet channel and an outlet formed at a position corresponding to the sample outlet channel, The sensor device is characterized in that the sample inlet channel is narrower and shorter than the sample outlet channel.

4. The sensor device according to any one of claims 1 to 3, A sensor device characterized in that a probe molecule is immobilized on the surface of the quartz crystal oscillator.

5. a quartz crystal unit having electrodes formed on its front and back surfaces and vibrating at a natural frequency f1 when a predetermined AC voltage is applied; a terminal portion electrically connected to the electrode; a frequency measurement unit that applies the predetermined AC voltage to the electrodes via the terminal unit and measures an actual oscillation frequency f2 of the quartz crystal resonator, the frequency measurement unit includes a reference oscillation unit that oscillates at a reference frequency f3, a first counter that measures the number of oscillations of the reference oscillation unit, and a second counter that measures the number of oscillations of the crystal oscillator, calculating the vibration frequency f2 based on a period t until the second number of measurements c2 of the second counter reaches a specified number of measurements c3, the first number of measurements c1 of the first counter, and the reference frequency f3; A sensor device, characterized in that the mass of a sample attached to the quartz crystal oscillator is calculated based on the natural frequency f1 and the vibration frequency f2.

6. The sensor device according to claim 5, The sensor device is characterized in that the specified number of times c3 is obtained by subtracting the number of times Δc corresponding to the sample and liquid attached to the quartz crystal oscillator from an initial setting value.

7. 7. The sensor device according to claim 5, The sensor device according to claim 1, wherein the first counter includes a first frequency dividing circuit that divides and measures the number of vibrations of the reference oscillator.

8. The sensor device according to any one of claims 5 to 7, The sensor device is characterized in that the second counter includes a second frequency divider circuit that divides and measures the number of oscillations of the crystal oscillator.

9. 9. The sensor device according to claim 5, A sensor device characterized in that the output of the reference oscillator is shared as a clock signal that synchronizes the entire circuit.

10. The sensor device according to any one of claims 5 to 9, A sensor device characterized in that a probe molecule is immobilized on the surface of the quartz crystal oscillator.

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