JP6908834B2 - Dielectric spectroscopy sensor and permittivity measurement method - Google Patents

Description

The present invention relates to a technique for measuring the complex permittivity of a trace amount of liquid sample.

As the population ages, dealing with adult diseases has become a major issue. Testing such as blood glucose level is a heavy burden on the patient because it requires blood sampling. Therefore, a non-invasive component concentration measuring device that does not collect blood is drawing attention.

As a non-invasive component concentration measuring device, electromagnetic waves in the microwave-millimeter wave band are less scattered in the living body than optical methods such as near-infrared light, and the energy of one photon is low. A method using is proposed.

For example, there is a method using the resonance structure shown in Non-Patent Document 1. In this method, a device having a high Q value such as an antenna or a resonator is brought into contact with a measurement sample, and the frequency characteristics around the resonance frequency are measured. Since the resonance frequency is determined by the complex permittivity around the device, the component concentration is estimated from the shift amount of the resonance frequency by predicting the correlation between the shift amount of the resonance frequency and the component concentration in advance.

As another method using electromagnetic waves in the microwave-millimeter wave band, the dielectric spectroscopy method shown in Patent Document 1 has been proposed. Dielectric spectroscopy irradiates the skin with electromagnetic waves, absorbs the electromagnetic waves according to the interaction between the blood component to be measured, for example, glucose molecules and water, and observes the amplitude and phase of the electromagnetic waves. The dielectric relaxation spectrum is calculated from the amplitude and phase of the observed electromagnetic wave with respect to the frequency. The dielectric relaxation spectrum is generally expressed as a linear combination of relaxation curves based on the Core-Cole equation, and the complex permittivity is calculated. In the measurement of biological components, for example, the complex permittivity has a correlation with the amount of blood components such as glucose and cholesterol contained in blood, and is measured as an electric signal (amplitude, phase) corresponding to the change. A calibration model is constructed by measuring the correlation between the change in the complex permittivity and the component concentration in advance, and the component concentration is calibrated from the measured change in the dielectric relaxation spectrum.

Regardless of which method is used, it is important to measure the change in permittivity in advance by wideband dielectric spectroscopy because the measurement sensitivity can be expected to improve by selecting a frequency band that has a strong correlation with the target component. Is.

Among the dielectric spectroscopy methods, it has been reported that dielectric spectroscopy in the DC-100 GHz band is obtained by dielectric spectroscopy using a device in which microchannels are integrated on a Coplanar line (CPW) as shown in Non-Patent Document 2. Moreover, since the amount of the sample can be measured with about several tens of μl, it is also suitable for the dielectric spectroscopic characteristics of expensive substances such as biological samples.

Japanese Unexamined Patent Publication No. 2013-32933

M. Hofmann, G. Fischer, R. Weigel, and D. Kissinger, "Microwave-Based Noninvasive Concentration Measurements for Biomedical Applications", IEEE Transactions on Microwave Theory and Techniques, May 2015, Vol. 16, No. 5, pp. 2195-2203 K.Grenier, D. Dubuc, PE. Poleni, M. Kumemura, H. Toshiyoshi, T. Fujii, and H. fujita, "Integrated Broadband Microwave and Microfluidic Sensor Dedicated to Bioengineering", IEEE Transactions on Microwave Theory and Techniques, December 2009, Vol. 57, No. 12, pp. 3246-3253

A conventional CPW type dielectric spectroscopy sensor is connected to a vector network analyzer (VNA) or an impedance analyzer (Impedance Analyzer: IA) via a high frequency probe such as a GSG probe. For this reason, there is a problem that the measurement reproducibility at the time of repeated measurement is lowered because the position of the probe varies depending on the measurer and the transmission characteristics change due to the CPW being damaged by the probe.

The present invention has been made in view of the above, and an object of the present invention is to measure the dielectric constant with good reproducibility in dielectric spectroscopy.

The first dielectric spectroscopic sensor according to the present invention includes a substrate on which a coplanar line is formed, a base material on which a microchannel for arranging a sample is formed, and a first high-frequency substrate having connectors arranged at both ends of the coplanar line. A second high-frequency board having a substrate on which a coplanar line is formed, a base material on which no microchannel is formed, connectors arranged at both ends of the coplanar line, and a coplanar line having a size half that of the second high-frequency board. It is characterized by having a third and fourth high frequency substrates for reflection measurement including a formed substrate, a base material not forming a microchannel, and a connector arranged at one end of the coplanar line.

The second method for measuring the dielectric constant according to the present invention includes a substrate on which a coplanar line is formed, a base material on which a microchannel for arranging a sample is formed, and a first high-frequency substrate having connectors arranged at both ends of the coplanar line. A second high-frequency board having a substrate on which a coplanar line is formed, a base material on which no microchannel is formed, and connectors arranged at both ends of the coplanar line, and a coplanar line that is half the size of the second high-frequency board. The dielectric spectroscopic sensor having a third and fourth high-frequency substrates for reflection measurement including a substrate on which a microchannel is formed, a base material on which a microchannel is not formed, and a connector arranged at one end of the coplanar line is used. A dielectric constant measuring method for measuring the dielectric constant of a sample, wherein the S parameter of the first high frequency substrate is measured in a state where the sample is not arranged in the microchannel, and the S parameter of the second high frequency substrate is measured. A step of measuring the S-parameters of the third and fourth high-frequency substrates, a step of calculating an error coefficient from the measured S-parameters using TRL calibration, and a sample placed in the microchannel. In this state, the S parameter of the first high frequency substrate is measured and the S parameter corrected by the error coefficient is calculated, the propagation constant is calculated based on the corrected S parameter, and the propagation constant is effective. It is characterized by having a step of calculating the dielectric constant and a step of calculating the dielectric constant of the sample from the effective dielectric constant.

According to the present invention, the dielectric constant can be measured with good reproducibility in dielectric spectroscopy.

It is a figure which shows the structure of the dielectric spectroscopic sensor which has two kinds of high frequency substrates in this embodiment. It is an exploded perspective view which shows the structure of the dielectric spectroscopic sensor in this embodiment. It is a flowchart which shows the flow of the process of measuring the dielectric constant of a sample. It is a figure which shows the structure of the dielectric spectroscopic sensor which has four kinds of high frequency substrates in this embodiment. It is a flowchart which shows the flow of the process of measuring the dielectric constant of a sample using the dielectric spectroscopic sensor of FIG.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.

FIG. 1 is a diagram showing a configuration of a dielectric spectroscopy sensor having two types of high-frequency substrates in the present embodiment. FIG. 1A is a high-frequency substrate 1A having a microchannel formed therein, and FIG. 1B is a high-frequency substrate 1B not forming a microchannel.

The high-frequency substrate 1A includes a substrate 11, a CPW 12, and a base material 13 on which a microchannel 14 is formed, and RF connectors 15 are mounted on both ends of the CPW 12.

The high-frequency substrate 1B includes a substrate 11, a CPW 12, and a base material 13 on which a microchannel 14 is not formed, and RF connectors 15 are mounted on both ends of the CPW 12.

Since the high-frequency substrates 1A and 1B are provided with the RF connector 15, measurement can be performed with good reproducibility and without damaging the metal pattern of CPW12.

Examples of the material of the substrate 11 include glass epoxy, Teflon, silicon (Si), alumina, quartz, glass, co-fired ceramics (LTCC), gallium arsenide and indium phosphorus.

The CPW 12 is formed on the substrate 11 so that its characteristic impedance is 50Ω. For example, when a glass epoxy substrate is used for the substrate 11, the signal line width of the CPW 12 is set to about 200 μm, and the gap between the signal line and the ground line is set to about 100 μm. The characteristic impedance Z of CPW can be calculated by the following equation (1).

Here, ε ₀ and μ ₀ are the permittivity and permeability of the vacuum, the function K (x) is the first-class elliptic integral with respect to the variable x, w is the signal line width of CPW, and g is the signal-ground line of CPW. The gap width, ε _sub, is the relative permittivity of the substrate.

However, when the substrate thickness is reduced to about 1 mm or less, a deviation is likely to occur between the value of the equation (1) and the actual characteristic impedance, so detailed parameters are determined by calculation by electromagnetic field analysis.

As the material of CPW 12, a material having good adhesion to the substrate 11, for example, copper, gold, aluminum, or the like is used.

As the RF connector 15, for example, a GPPO, G3PO, SMA, K, 2.4 mm, V, 1 mm connector or the like is used.

The base material 13 is integrated on the substrate 11. Examples of the base material 13 include PMMA (polymethylmethacrylate resin) and PDMS (polydimethylsiloxane). The base material 13 and the substrate 11 are adhered to each other with a double-sided tape having a thickness of about 25 to 300 μm.

In the high frequency substrate 1A, the microchannel 14 is formed in the center of the base material 13. The micro flow path 14 can be formed by cutting off the center of the double-sided tape. Alternatively, it can also be formed by cutting the central portion of the base material 13 to which the double-sided tape is adhered with a laser cutter or the like. The substrate 11 and the base material 13 are adhered so that the microchannel 14 and the central portion of the substrate 11 coincide with each other. The width of the micro flow path 14 is about 500 μm to 1 mm.

In the high-frequency substrate 1B, only the base material 13 is integrated without forming the microchannel 14. The length of the base material 13 of the high-frequency substrate 1B is the length obtained by subtracting the width of the microchannel 14 from the length of the base material 13 of the high-frequency substrate 1A.

The length of the high frequency substrate 1A is such that the length of the CPW 12 is about 5 mm to 20 mm, excluding the RF connector 15. The length of the high-frequency substrate 1B is the length obtained by subtracting the width of the microchannel 14 from the length of the high-frequency substrate 1A. The width of the high frequency substrates 1A and 1B shall be at least twice the width of the entire CPW12.

As shown in the exploded perspective view of FIG. 2, the accuracy of integration is improved by providing the alignment pattern and the alignment guide hole. In the example of FIG. 2, the size of the substrate 11, the base material 13, and the double-sided tape 16 are the same, and a guide hole for inserting the positioning pin 17 is provided.

Next, the measurement of the dielectric constant of the sample will be described.

FIG. 3 is a flowchart showing a flow of processing for measuring the dielectric constant of a sample.

The S-parameters of the high-frequency substrates 1A and 1B are measured (steps S11 and S12). The high-frequency substrate 1A measures the S parameter in a state where the liquid sample whose dielectric constant is to be measured is placed in the microchannel 14. For the measurement of S parameter, for example, VNA can be used. An instrument capable of measuring the impedance of a two-terminal circuit such as an impedance analyzer may be used.

The propagation constant γ is calculated using the measured S-parameters (step S13). Using the S-parameters of the high-frequency substrate 1A [S ^line ₁₁ S ^line ₁₂ S ^line ₂₁ S- ^line ₂₂ ] and the S-parameters of the high-frequency substrate 1B [S ^thru ₁₁ S ^thru ₁₂ S ^thru ₂₁ S ^thru ₂₂ ], the propagation constant γ is as follows. It can be obtained by the formula (2).

L _fluid is the flow path length.

_{The effective permittivity ε eff} is calculated from the obtained propagation constant γ (step S14). The effective permittivity ε _eff can be obtained by the following equation (3).

The permittivity ε _{m of the} sample is calculated from the effective permittivity ε _eff (step S15). The effective dielectric constant epsilon _eff is a value of a dielectric constant epsilon _m of the dielectric constant epsilon _sub and the sample substrate of the sensor, the dielectric constant epsilon _m of the sample can be derived using the following equation (4).

Alternatively, α and β satisfying the following equation (5) are derived in advance by electromagnetic field simulation and converted.

When the substrate is a thin film or the structure is such that the metal film thickness of CPW cannot be ignored, the relationship of the equation (4) does not hold, so the conversion method using the equation (5) is effective.

The above calculation process may be executed by a computer.

Next, another dielectric spectroscopy sensor will be described.

FIG. 4 is a diagram showing a configuration of a dielectric spectroscopy sensor having four types of high-frequency substrates in the present embodiment. The dielectric spectroscopy sensor shown in FIG. 1 is obtained by adding high-frequency substrates 1C and 1D for reflection measurement to the high-frequency substrates 1A and 1B shown in FIG.

In the high frequency substrates 1C and 1D shown in FIGS. 4C and 4D, the RF connector 15 is mounted only on one end surface of the CPW12. The length of the high frequency substrates 1C and 1D is half the length of the high frequency substrate 1B. The high frequency substrates 1C and 1D can be manufactured by cutting the high frequency substrate 1A or the high frequency substrate 1B.

The base material 13 is adhered to the substrate so that the end face of the RF connector 15 on the non-mounted side and the end face of the base material 13 coincide with each other.

By using substrates processed in the same lot for the high-frequency substrates 1A to 1D, it can be expected that deterioration of measurement accuracy due to variations in each product can be suppressed.

Next, the measurement of the dielectric constant of the sample using four types of high-frequency substrates will be described.

FIG. 5 is a flowchart showing a flow of processing for measuring the dielectric constant of a sample using four types of high-frequency substrates.

The S-parameters of the high-frequency substrates 1A to 1D are measured (steps S21 to S23). The high-frequency substrate 1A measures S-parameters without a sample placed.

Assuming that the measurement results of steps S21, S22, and S23 are thru, reflect, and line, the error coefficient is calculated using TRL calibration (step S24).

After measuring the S-parameters of the high-frequency substrate 1A on which the sample is placed (step S25), the S-parameters in the flow path with the error coefficient corrected are calculated (step S26), and the propagation constant γ is calculated using the S-parameters (step S26). Step S27).

_{The matrix T fluid obtained} by converting the corrected S parameter into a T parameter is represented by the following equation (6).

Therefore, the propagation constant γ of the flow path portion can be expressed by the following equation (7) from the _{derived T fluid.}

_{After that, the effective permittivity ε eff} is calculated and the permittivity ε _{m of the} sample is calculated in the same manner as when the high frequency substrates 1A and 1B of FIG. 1 are used (steps S28 and S29).

As described above, according to the present embodiment, the substrate 11 on which the coplanar line (CPW) 12 is formed, the base material 13 on which the microchannel 14 for arranging the sample is formed, and the RF connector 15 mounted on both ends of the CPW 12 High-frequency substrate 1A using a dielectric spectroscopic sensor having a high-frequency substrate 1A provided with a CPW 12, a base material 13 not forming a microchannel 14 and a high-frequency substrate 1B provided with an RF connector 15. , 1B S-parameters are measured, the propagation constant is calculated based on the measured S-parameters, the effective dielectric constant is calculated from the propagation constant, and the dielectric constant of the sample is calculated from the effective dielectric constant. By de-embedding the transmission characteristics of the CPW12, it is possible to measure the dielectric constant with good reproducibility in dielectric spectroscopy. Since the high-frequency substrates 1A and 1B of the present embodiment include the RF connector 15, it is possible to prevent the position of the probe from being uneven by the measurer and the CPW 12 from being damaged by the probe.

According to this embodiment, TRL calibration is performed from the measurement results of S-parameters of high-frequency substrates 1A to 1D using a dielectric spectroscopy sensor having high-frequency substrates 1C and 1D for reflection measurement in addition to high-frequency substrates 1A and 1B. The error coefficient is calculated using, the S parameter corrected for the error coefficient is calculated from the measurement result of the S parameter of the high frequency substrate 1A on which the sample is placed, the propagation constant is calculated using the corrected S parameter, and the propagation constant is used. By calculating the effective dielectric constant and calculating the dielectric constant of the sample from the effective dielectric constant, it is possible to measure the dielectric constant with good reproducibility in dielectric spectroscopy.

1A to 1D ... High frequency board 11 ... Board 12 ... CPW
13 ... Base material 14 ... Micro flow path 15 ... RF connector 16 ... Double-sided tape 17 ... Positioning pin

Claims (2)

A substrate on which a coplanar line is formed, a base material on which a microchannel for arranging a sample is formed, and a first high-frequency substrate having connectors arranged at both ends of the coplanar line.
A substrate on which a coplanar line is formed, a base material on which no microchannel is formed, and a second high-frequency substrate having connectors arranged at both ends of the coplanar line.
The third and third for reflection measurement provided with a substrate having a coplanar line formed to be half the size of the second high-frequency substrate, a base material not forming a microchannel, and a connector arranged at one end of the coplanar line. 4 high frequency board and
A dielectric spectroscopic sensor characterized by having. A substrate on which a coplanar line is formed, a first high-frequency board having a base material on which a microchannel for arranging a sample is formed, connectors arranged at both ends of the coplanar line, and a substrate on which a coplanar line is formed and a microchannel are formed. A second high-frequency board having a base material and connectors arranged at both ends of the coplanar line, and a board having a coplanar line half the size of the second high-frequency board do not form a microchannel. A dielectric constant measuring method for measuring the dielectric constant of a sample using a dielectric spectroscopic sensor having a base material and a third and fourth high frequency substrates for reflection measurement having a connector arranged at one end of the coplanar line. hand,
A step of measuring the S parameter of the first high frequency substrate in a state where the sample is not arranged in the microchannel, and a step of measuring the S parameter.
The step of measuring the S parameter of the second high frequency substrate and
The step of measuring the S-parameters of the third and fourth high-frequency substrates, and
The step of calculating the error coefficient from the measured S-parameters using TRL calibration, and
A step of measuring the S-parameters of the first high-frequency substrate with the sample placed in the microchannel and calculating the S-parameters corrected by the error coefficient.
The step of calculating the propagation constant based on the corrected S parameter, and
The step of calculating the effective permittivity from the propagation constant and
The step of calculating the permittivity of the sample from the effective permittivity, and
A method for measuring a dielectric constant.

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