Management method, measurement method, measurement device, quartz crystal oscillator sensor, and kit

Abstract

The present invention provides a management method, measurement method, measurement device, quartz crystal oscillator sensor, and kit for more easily managing the purity of a chemical solution containing an organic solvent. The management method of the present invention senses impurities in a chemical solution containing an organic solvent to manage the purity of the chemical solution. The management method comprises: step 1 of preparing a target chemical solution containing an organic solvent; step 2 of bringing a quartz crystal oscillator sensor containing an adsorption layer that adsorbs impurities and a quartz crystal oscillator into contact with the target chemical solution to obtain a change in the resonant frequency of the quartz crystal oscillator caused by contact with the target chemical solution; and step 3 of comparing the obtained change in resonant frequency to determine whether it falls within a predetermined allowable range of resonant frequency change based on the purity of the target chemical solution, thereby managing the purity of the chemical solution. In step 2, at least a portion of the liquid contact portion that contacts the target chemical solution is formed of a fluorine-based resin.

Description

Technical Field

[0001] The present invention relates to a management method, a measuring method, a measuring device, a quartz crystal oscillator sensor and a kit. Background Art

[0002] The manufacturing process of semiconductor devices includes various steps such as photolithography, etching, ion implantation, and stripping. The various chemical solutions used in these semiconductor device manufacturing steps are required to be of high purity, such as developers, rinsers, pre-wet solutions, and strippers.

[0003] One method of evaluating the characteristics of a high-purity chemical solution is to apply the high-purity chemical solution on a substrate and measure the number of defects on the substrate to evaluate the characteristics of the chemical solution.

[0004] For example, in Patent Document 1, the above-mentioned evaluation is performed using a surface inspection device (SP-5; manufactured by KLA Tencor).

[0005] Previous technical literature

[0006] Patent Literature

[0007] Patent Document 1: International Publication No. 2017 / 169834 Summary of the Invention

[0008] Technical issues to be solved by the invention

[0009] On the other hand, in the measurement using the surface inspection apparatus (SP-5; manufactured by KLA Tencor) described in Patent Document 1, the measurement procedure itself is complicated and the operation time is long, resulting in poor versatility.

[0010] Therefore, it is not preferable from an industrial point of view to measure the purity of a chemical solution by performing the above-mentioned measurement during the production of the chemical solution, and a method for more simply managing the purity of the produced chemical solution is desired.

[0011] In view of the above-mentioned actual situation, an object of the present invention is to provide a method for more simply managing the purity of a chemical solution containing an organic solvent.

[0012] Furthermore, an object of the present invention is to provide a measurement method, a measurement device, a quartz crystal oscillator sensor, and a kit.

[0013] Means for solving technical problems

[0014] As a result of intensive research, the present inventors have found that the above-mentioned problems can be solved by the following configuration.

[0015] (1) A management method for managing the purity of a chemical solution containing an organic solvent by sensing impurities in the chemical solution, the management method comprising:

[0016] Step 1: preparing a target drug solution containing an organic solvent;

[0017] Step 2: bringing a quartz crystal oscillator sensor including an adsorption layer for adsorbing impurities and a quartz crystal oscillator into contact with a target chemical solution, and obtaining a change in the resonant frequency of the quartz crystal oscillator caused by the contact with the target chemical solution; and

[0018] Step 3: Comparing the obtained change in resonance frequency to see if it is within a preset allowable range of change in resonance frequency based on the purity of the target chemical solution to manage the purity of the chemical solution.

[0019] In step 2, at least a portion of the liquid contact portion that comes into contact with the target chemical solution is formed of a fluorine-based resin.

[0020] (2) The management method according to (1), wherein:

[0021] A target chemical solution is fed to the quartz crystal oscillator sensor so that the target chemical solution comes into contact with the quartz crystal oscillator sensor.

[0022] (3) The management method according to (1) or (2), wherein:

[0023] The target chemical solution is made to flow toward the quartz crystal oscillator sensor in one direction, so that the target chemical solution comes into contact with the quartz crystal oscillator sensor.

[0024] (4) The management method according to any one of (1) to (3), wherein

[0025] The target chemical solution is circulated and supplied to the quartz crystal oscillator sensor. The circulation flow rate of the target chemical solution is 0.01 to 1000 ml / s.

[0026] (5) The management method according to any one of (1) to (4), wherein

[0027] The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

[0028] (6) The management method according to any one of (1) to (5), wherein

[0029] The quartz crystal oscillator sensor has multiple adsorption layers.

[0030] Step 2 is a step of obtaining the change in resonance frequency for each of the plurality of adsorption layers.

[0031] Step 3 is a step of managing the purity of the target chemical solution by calculating the difference in the amount of change in the resonance frequency of each of the plurality of adsorption layers and comparing the obtained value to see whether it is within a preset allowable range of the amount of change in the resonance frequency based on the purity of the target chemical solution.

[0032] (7) The management method according to (6), wherein:

[0033] At least one of the plurality of adsorption layers is an Au layer.

[0034] (8) A method for measuring a drug solution, comprising:

[0035] Step 1, preparing a target drug solution containing an organic solvent; and

[0036] Step 2: bringing a quartz crystal oscillator sensor including an adsorption layer for adsorbing impurities in a target chemical solution and a quartz crystal oscillator into contact with the target chemical solution, and obtaining a change in the resonant frequency of the quartz crystal oscillator caused by the contact with the target chemical solution.

[0037] In step 2, at least a portion of the liquid contact portion that comes into contact with the target chemical solution is formed of a fluorine-based resin.

[0038] (9) The measuring method according to (8), wherein

[0039] A target chemical solution is fed to the quartz crystal oscillator sensor so that the target chemical solution comes into contact with the quartz crystal oscillator sensor.

[0040] (10) The measuring method according to (8) or (9), wherein

[0041] The target chemical solution is made to flow toward the quartz crystal oscillator sensor in one direction, and the target chemical solution is made to contact the quartz crystal oscillator sensor.

[0042] (11) The measuring method according to any one of (8) to (10), wherein

[0043] The target chemical solution is circulated and supplied to the quartz crystal oscillator sensor. The circulation flow rate of the target chemical solution is 0.01 to 1000 ml / s.

[0044] (12) The measuring method according to any one of (8) to (11), wherein

[0045] The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

[0046] (13) The measuring method according to any one of (8) to (12), wherein

[0047] The quartz crystal oscillator sensor has multiple adsorption layers.

[0048] Step 2 is a step of obtaining the amount of change in the resonance frequency for each of the plurality of adsorption layers.

[0049] (14) The measuring method according to (13), wherein

[0050] At least one of the plurality of adsorption layers is an Au layer.

[0051] (15) A measuring device for sensing impurities in a liquid medicine containing an organic solvent, the measuring device comprising:

[0052] A quartz crystal oscillator sensor, which contacts a target chemical solution containing an organic solvent and includes an adsorption layer for adsorbing impurities and a quartz crystal oscillator;

[0053] an oscillating portion that vibrates the quartz crystal resonator at a resonant frequency;

[0054] a detection unit connected to the quartz crystal oscillator sensor and detecting a change in the resonance frequency of the quartz crystal oscillator caused by contact with the target chemical solution; and

[0055] The supply unit supplies the target chemical solution to the quartz crystal oscillator sensor so that the target chemical solution comes into contact with the quartz crystal oscillator sensor.

[0056] At least a portion of the liquid contact portion that comes into contact with the target drug solution is made of a fluorine-based resin.

[0057] (16) The measuring device according to (15), further comprising a display unit for displaying the amount of change in the resonance frequency.

[0058] (17) The measuring device according to (15) or (16), wherein

[0059] The supply unit supplies the target chemical solution to the quartz crystal oscillator sensor by causing the target chemical solution to flow in one direction.

[0060] (18) The measuring device according to any one of (15) to (17), wherein

[0061] The supply unit circulates the target chemical solution and supplies it to the quartz crystal oscillator sensor. The circulation flow rate of the target chemical solution is 0.01 to 1000 ml / s.

[0062] (19) The measuring device according to any one of (15) to (18), wherein

[0063] The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

[0064] (20) The measuring device according to any one of (15) to (19), wherein

[0065] The quartz crystal oscillator sensor has multiple adsorption layers.

[0066] The detection unit detects the amount of change in the resonant frequency of each of the plurality of adsorption layers.

[0067] (21) The measuring device according to (20), wherein

[0068] At least one of the plurality of adsorption layers is an Au layer.

[0069] (22) The measuring device according to any one of (15) to (21), further comprising:

[0070] A sealing portion, configured on the quartz crystal oscillator sensor;

[0071] a block body, which is arranged on the quartz crystal oscillator sensor via a sealing portion and is provided with a supply channel for supplying the target chemical liquid to the quartz crystal oscillator sensor and a discharge channel for discharging the target chemical liquid from the quartz crystal oscillator sensor; and

[0072] The liquid delivery part is composed of a first hose connected to the supply channel and a second hose connected to the discharge channel.

[0073] At least one of the liquid contact portion of the seal portion in contact with the target drug liquid, the liquid contact portion of the block portion in contact with the target drug liquid, and the liquid contact portion of the liquid delivery portion in contact with the target drug liquid is formed of a fluorine-based resin.

[0074] (23) The measuring device according to (22), wherein

[0075] The liquid contact portion of the block that contacts the target drug solution is made of a fluorine-based resin having a tensile strength of 20 to 60 MPa and a Shore D hardness of 60 to 80.

[0076] (24) The measuring device according to (22) or (23), wherein

[0077] The liquid contact portion of the block that contacts the target drug solution is formed of a fluorine-based resin selected from the group consisting of perfluoroalkoxyalkanes, ethylene tetrafluoroethylene copolymers, perfluoroethylene propylene copolymers, polychlorotrifluoroethylene, and polyvinylidene fluoride.

[0078] (25) The measuring device according to (22), wherein

[0079] The liquid contact portion of the liquid delivery portion that comes into contact with the target drug solution is composed of a fluorine-based resin having repeating units containing fluorine atoms, carbon atoms, and atoms other than fluorine atoms and carbon atoms.

[0080] (26) The measuring device according to (22) or (25), wherein

[0081] The liquid contact portion of the liquid delivery portion that contacts the target drug solution is formed of a fluorine-based resin selected from the group consisting of a ternary copolymer of tetrafluoroethylene, hexafluoropropylene, and vinylidene fluoride, polyvinylidene fluoride, an ethylene tetrafluoroethylene copolymer, and polychlorotrifluoroethylene.

[0082] (27) The measuring device according to (22), wherein

[0083] The liquid contact portion of the sealing portion that contacts the target drug solution is made of a fluorine-based resin having a tensile strength of 20 to 40 MPa, a Shore D hardness of 56 to 70, and a flexural modulus of 0.5 to 3 GPa.

[0084] (28) The measuring device according to (22) or (27), wherein

[0085] The liquid contact portion of the sealing portion that contacts the target drug solution is formed of a fluorine-based resin selected from the group consisting of perfluoroalkoxyalkanes, perfluoroethylene-propylene copolymers, ethylene-chlorotrifluoroethylene copolymers, ethylene-tetrafluoroethylene copolymers, polychlorotrifluoroethylene, and polyvinylidene fluoride.

[0086] (29) A quartz crystal oscillator sensor used in a measuring device according to any one of (15) to (28), wherein the quartz crystal oscillator sensor comprises a quartz crystal oscillator and an adsorption layer disposed on the quartz crystal oscillator.

[0087] The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

[0088] (30) The quartz crystal oscillator sensor according to (29), wherein:

[0089] At least two adsorption layers are arranged on the quartz crystal oscillator.

[0090] (31) The quartz crystal oscillator sensor according to (30), wherein:

[0091] At least one of the plurality of adsorption layers is an Au layer.

[0092] (32) A kit comprising a medical solution and an information display unit that displays or stores information on the resonance frequency of the medical solution,

[0093] A change in the resonant frequency of a quartz crystal oscillator resulting from contact between a chemical solution and an adsorption layer containing impurities adsorbed in the chemical solution and a quartz crystal oscillator sensor is obtained, the obtained change in resonant frequency is compared with a change in resonant frequency based on a predetermined purity of the chemical solution, an evaluation of the purity of the chemical solution relative to the obtained change in resonant frequency is provided, and a correlation is established between the obtained change in resonant frequency and the purity of the chemical solution based on the evaluation, and the correlation is recorded as resonant frequency information of the chemical solution.

[0094] The resonance frequency information of the chemical solution is used to obtain information on the purity of the chemical solution.

[0095] (33) The kit according to (32), comprising a container for storing a medical solution,

[0096] The information display portion is provided on the container.

[0097] (34) The kit according to (32) or (33), wherein:

[0098] The resonance frequency information of the medical solution is displayed on the information display unit using at least one of characters, symbols, and barcodes.

[0099] Effects of the Invention

[0100] According to the present invention, a method for more simply managing the purity of a chemical solution containing an organic solvent can be provided.

[0101] Furthermore, according to the present invention, a measuring method, a measuring device, a quartz crystal oscillator sensor, and a kit can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0102] Figure 1 This is a schematic diagram showing an example of a measuring device according to an embodiment of the present invention.

[0103] Figure 2 This is a schematic cross-sectional view showing a first example of a quartz crystal oscillator sensor according to an embodiment of the present invention.

[0104] Figure 3 This is a graph showing an example of a calibration curve showing the relationship between the amount of impurities and the resonant frequency of a quartz crystal oscillator.

[0105] Figure 4 This is a schematic diagram showing an example of a flow cell unit of a measurement device according to an embodiment of the present invention.

[0106] Figure 5 This is a schematic diagram showing a second example of the quartz crystal oscillator sensor according to the embodiment of the present invention.

[0107] Figure 6This is a schematic cross-sectional view showing a second example of the quartz crystal oscillator sensor according to the embodiment of the present invention.

[0108] Figure 7 This is a schematic diagram showing a third example of the quartz crystal oscillator sensor according to the embodiment of the present invention.

[0109] Figure 8 This is a schematic cross-sectional view showing a third example of the quartz crystal oscillator sensor according to the embodiment of the present invention.

[0110] Figure 9 This is a schematic perspective view showing an example of a kit according to an embodiment of the present invention.

[0111] Figure 10 This is a schematic diagram showing an example of the information display unit of the kit according to the embodiment of the present invention.

[0112] Figure 11 This is a graph in which the results of Example A are plotted on rectangular coordinates with the amount of change in resonance frequency as the horizontal axis and the number of defects as the vertical axis. DETAILED DESCRIPTION

[0113] Hereinafter, the management method, measurement method, measurement device, quartz crystal oscillator sensor, and kit of the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings.

[0114] In addition, the drawings described below are exemplary drawings for explaining the present invention, and the present invention is not limited to the drawings shown below.

[0115] In the following, "to" indicating a numerical range includes the values ​​on both sides. For example, "ε is a value d to a value β" means that the range of ε is a range including the values ​​d and β, and in mathematical notation, d≤ε≤β.

[0116] [Measurement device]

[0117] Figure 1 is a schematic diagram showing an example of a measuring device according to an embodiment of the present invention, Figure 2 This is a schematic cross-sectional view showing a first example of a quartz crystal oscillator sensor according to an embodiment of the present invention.

[0118] Figure 1 The measuring device 10 shown is a device for sensing impurities in a drug solution containing an organic solvent. The measuring device 10 can be used to manage the purity of the target drug solution.

[0119] The measuring device 10 includes a flow cell unit 12, an oscillating unit 14, a detecting unit 15, a calculating unit 16, a memory 18, a supply unit 20, and a control unit 22. The measuring device 10 also includes a display unit 23, an output unit 24, and an input unit 25.

[0120] The control unit 22 controls the operation of the flow cell unit 12, the oscillating unit 14, the detecting unit 15, the calculating unit 16, the memory 18, and the supply unit 20. Furthermore, the control unit 22 controls the various components of the measuring device 10 based on the control of the operation of the display unit 23 and the output unit 24 and the input information from the input unit 25.

[0121] The flow cell unit 12 has an adsorption layer 34 containing adsorbed impurities (refer to Figure 2 ) and quartz crystal oscillator 27 (reference Figure 2 ) and a temperature adjustment unit 28 for maintaining the liquid temperature of the target chemical solution supplied to the flow cell unit 12. The flow cell unit 12 will be described in detail later.

[0122] The oscillator 14 is electrically connected to the quartz crystal oscillator sensor 26. The oscillator 14 vibrates the quartz crystal oscillator 27 at a resonance frequency. The oscillator 14 applies a high-frequency sinusoidal signal as a frequency signal to the quartz crystal oscillator sensor 26 and includes an oscillation circuit (not shown).

[0123] Furthermore, the detection unit 15 is electrically connected to the oscillator 14. The detection unit 15 measures the resonant frequency of the quartz crystal oscillator 27 and detects the change in the resonant frequency of the quartz crystal oscillator caused by contact with the target chemical solution. Alternatively, the detection unit 15 may detect the difference in the change in resonant frequency obtained by using multiple adsorption layers, as described later.

[0124] The detection unit 15 reads the frequency signal from the oscillation unit 14, samples the frequency signal every second, for example, and stores the data as time series data in the memory 18. Furthermore, the measurement time and the frequency tolerance are stored in the memory 18. The detection unit 15 measures the resonant frequency of the quartz crystal oscillator 27 based on the measurement time and the frequency tolerance, and detects the change in the resonant frequency of the quartz crystal oscillator caused by contact with the target chemical solution.

[0125] The measurement time refers to the time required to obtain the change in resonant frequency caused by contact between impurities and adsorption layer 34. The measurement time is not particularly limited and is appropriately determined based on factors such as the supply flow rate of the target chemical solution. For example, it is preferably 10 minutes or longer, and more preferably 30 minutes or longer. The upper limit is not particularly limited, but from the perspective of productivity, it is preferably 3 hours or shorter, and more preferably 2 hours or shorter.

[0126] The frequency tolerance is a threshold used to determine whether the value serving as an indicator of frequency stabilization is sufficiently small to be considered stable when determining whether the frequency is stable. The frequency tolerance is, for example, a value appropriately set based on the set measurement sensitivity. For example, when the resonance frequency is 30 MHz and the measurement sensitivity is 5 Hz, the allowable error range within the measurement time is set to 0.5 Hz. This is equivalent to 0.0167 ppm. The tolerance corresponding to this error range is 1.67 × 10 -8 (0.0167ppm) or less.

[0127] In the detection unit 15, the frequency is detected, for example, by a frequency counter, which is a well-known circuit. Alternatively, the frequency may be detected by performing analog-to-digital conversion on a frequency signal, performing carrier shift processing to generate a rotating vector rotating at the frequency of the frequency signal, and determining the speed of the rotating vector, as described in Japanese Patent Application Laid-Open No. 2006-258787. This digital processing is preferably used in the detection unit 15 because it allows for high frequency detection accuracy.

[0128] Calculation unit 16 reads the preset permissible range of resonance frequency change based on the purity of the target medicinal solution stored in memory 18, compares the permissible range of resonance frequency change stored in memory 18 with the resonance frequency change obtained by detection unit 15, and manages the purity of the medicinal solution. For example, if the comparison is within the permissible range, the display unit 23 indicates that the purity of the medicinal solution is within the permissible range. On the other hand, if the comparison is outside the permissible range, the display unit 23 indicates that the purity of the medicinal solution is outside the permissible range. Alternatively, if the comparison is within the permissible range, the display unit 23 may indicate that the purity of the medicinal solution is outside the permissible range. Alternatively, if the comparison is outside the permissible range, the display unit 23 may indicate that the purity of the medicinal solution is outside the permissible range.

[0129] Memory 18 stores the change in resonant frequency based on the previously set purity of the target chemical solution and its allowable range. In addition, memory 18 may also store the resonant frequency of a quartz crystal oscillator. As described later, in a configuration in which multiple electrodes are provided on the quartz crystal oscillator, the resonant frequency of each electrode and the difference in resonant frequency between electrodes may also be stored.

[0130] In addition, regarding the change amount of the resonance frequency stored in the memory 18, for example, Figure 3 As shown, a calibration curve L is obtained that represents the relationship between the amount of impurities in a specific target chemical solution and the resonant frequency of the quartz crystal oscillator 27. Based on this calibration curve L, the relationship between the amount of impurities in the specific target chemical solution and the change in the resonant frequency can be obtained. Furthermore, by setting an allowable range for the calibration curve L, the allowable range for the change in the resonant frequency can be set. Figure 3 The impurity amount shown in the calibration curve L is, for example, measured using a surface inspection device. More specifically, after applying a predetermined amount of the target chemical solution to a predetermined substrate (e.g., a silicon wafer), the number of defects on the substrate coated with the target chemical solution is measured using the surface inspection device. The obtained number of defects can be used as the impurity amount.

[0131] Another example of a surface inspection device is one that irradiates a substrate coated with a target chemical solution with a laser beam, detects the laser beam scattered by defects on the substrate, and detects impurities on the substrate. Measurements are performed while the substrate is rotated during laser irradiation, enabling the coordinates of the defect to be inferred from the substrate's rotation angle and the radial position of the laser beam. An example of such a device is the "SP-5" manufactured by KLA Tencor, but other surface inspection devices with resolutions exceeding that of the "SP-5" are also possible (typically, successors to the "SP-5," etc.).

[0132] The display unit 23 displays the change in the resonant frequency obtained by the calculation unit 16 and is comprised of, for example, a display. The display is not particularly limited as long as it can display characters and images, and a liquid crystal display device, etc., may be used. Furthermore, the display on the display unit 23 is not limited to the change in the resonant frequency obtained; it may be the resonant frequency itself, or the difference in the change in multiple resonant frequencies obtained by using multiple adsorption layers, as described later. It may also display various settings and input information set by the measurement device 10.

[0133] The output unit 24 displays the obtained resonant frequency change or resonant frequency on a medium. More specifically, the display is performed using at least one of characters, symbols, and barcodes. The output unit 24 is configured by a printer or the like. The output unit 24 provides an information display unit that displays resonant frequency information of the medical solution in the kit, described later.

[0134] The input unit 25 is a variety of input devices such as a mouse and a keyboard for inputting various information by an operator's command. For example, the measurement device 10 is set up and data is loaded from the memory 18 via the input unit 25 .

[0135] In addition, the input unit 25 also includes an interface for inputting information stored in the memory 18 , and the information is stored in the memory 18 via an external storage medium or the like.

[0136] Furthermore, the measuring device 10 only needs to be able to obtain the change in the obtained resonant frequency, and does not necessarily require any other configuration. Thus, for example, while the calculation unit 16 is required in the management method, the measuring device 10 that obtains the change in the resonant frequency does not necessarily require the calculation unit 16.

[0137] The circulation cell unit 12 is a sensing unit that senses impurities in a liquid medicine containing an organic solvent. The circulation cell unit 12 is connected to the supply unit 20 using a first hose 29a and a second hose 29b. The target liquid medicine passes through the first hose 29a via the supply unit 20, and the target liquid medicine is supplied to a quartz crystal oscillator, which causes the target liquid medicine to pass through the second hose 29b and recovers the target liquid medicine. The supply unit 20 passes the target liquid medicine through the first hose 29a and the second hose 29b without contacting the target liquid medicine, for example, using a peristaltic pump. The supply unit 20 is not particularly limited as long as it can deliver the liquid without contacting the target liquid medicine, and for example, a syringe pump can be used.

[0138] The temperature control unit 28 includes, for example, a Peltier element. The Peltier element maintains the temperature of the target chemical solution. This allows the temperature of the target chemical solution to be kept constant, and the viscosity of the target chemical solution to be kept within a constant range. This reduces fluctuations in purity measurement conditions. The structure of the temperature control unit 28 is not particularly limited, as long as it can maintain the temperature of the target chemical solution.

[0139] [Quartz crystal oscillator sensor]

[0140] As described above, the quartz crystal oscillator sensor 26 includes the quartz crystal oscillator 27 . The quartz crystal oscillator 27 is, for example, disk-shaped. The electrodes 30 are provided on the front surface 27 a of the quartz crystal oscillator 27 , and the electrodes 31 are provided on the back surface 27 b of the quartz crystal oscillator 27 .

[0141] An adsorption layer 34 having impurities adsorbed thereon is provided on a surface 30a of an electrode 30 provided on a surface 27a of the quartz crystal resonator 27. The adsorption layer 34 is in contact with a target chemical solution containing an organic solvent.

[0142] As the quartz crystal oscillator 27, for example, an AT-cut quartz crystal oscillator is used. The AT-cut quartz crystal oscillator is an oscillator cut at an angle of 35°15′ from the Z axis of an artificial quartz crystal. The quartz crystal oscillator sensor 26 is not limited to Figure 2 The structure shown.

[0143] Oscillator 14 is electrically connected to electrodes 30 and 31. Oscillator 14 applies a high-frequency sinusoidal signal as a frequency signal to electrodes 30 and 31 and includes, for example, an oscillation circuit. Oscillator 14 causes quartz crystal oscillator 27 to vibrate at a resonant frequency. The resonant frequency of quartz crystal oscillator 27 is, for example, 27 MHz or 30 MHz.

[0144] The adsorption layer 34 is composed of, for example, at least one material selected from Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition. The type of impurities that are easily adsorbed varies depending on the material constituting the adsorption layer. Therefore, for example, when the amount of impurities in the target chemical solution is determined using the surface inspection device described above, and a corresponding correlation is established between the number of defects and the change in the resonant frequency, the substrate coated with the chemical solution used to measure the number of defects using the surface inspection device and the adsorption layer are preferably composed of the same material. That is, when a Si layer is used as the adsorption layer, a Si substrate (silicon wafer) is preferably used as the substrate.

[0145] The adsorption layer 34 can be formed by a vapor phase method such as sputtering or CVD (chemical vapor deposition), or a coating method.

[0146] The type of photosensitive resin composition is not particularly limited, and known photosensitive resin compositions may be used. Components contained in the photosensitive resin composition include, for example, a resin having a group that generates a polar group upon the action of an acid, and a photoacid generator. The photosensitive resin composition may further contain a basic compound, a hydrophobic resin, and the like.

[0147] In the quartz crystal oscillator sensor 26, the resonant frequency of the quartz crystal oscillator 27 changes depending on the amount of impurities adsorbed on the adsorption layer 34. By measuring the resonant frequency before and after contact with the target liquid, the change in the resonant frequency can be obtained. In addition, the change ΔF of the resonant frequency of the quartz crystal oscillator 27 can be expressed by the following formula called the Sauerbrey formula. In the following formula, F0 is the resonant frequency, Δm is the mass change, ρ is the density of the quartz crystal, μ is the shear stress of the quartz crystal, and A is the area of ​​the electrode. According to the following formula, by increasing the resonant frequency F0 of the quartz crystal oscillator, the mass detection sensitivity can be improved, that is, the measurement accuracy of impurities can be improved.

[0148] [Formula 1]

[0149]

[0150] [Flow cell unit]

[0151] Figure 4 This is a schematic diagram showing an example of a flow cell unit of a measurement device according to an embodiment of the present invention.

[0152] In the flow cell unit 12, for example, a quartz crystal oscillator sensor 26 is arranged on the temperature regulating portion 28 via a sealing portion 43. A sealing portion 42 is provided on the quartz crystal oscillator sensor 26 along the periphery of the quartz crystal oscillator 27. A block 40 is arranged on the sealing portion 42. A supply channel 40a for supplying the target liquid medicine to the quartz crystal oscillator sensor 26 is provided in the block 40. The supply channel 40a is connected to the first hose 29a. In addition, a discharge channel 40b for discharging the target liquid medicine from the quartz crystal oscillator sensor 26 is provided in the block 40. The discharge channel 40b is connected to the second hose 29b. That is, the circulation pool unit 12 also has: a sealing portion 42, which is arranged on the quartz crystal oscillator sensor 26; a block 40, which is arranged on the quartz crystal oscillator sensor 26 via the sealing portion 42, and is provided with a supply channel 40a for supplying the target drug solution to the quartz crystal oscillator sensor 26 and a discharge channel 40b for discharging the target drug solution from the quartz crystal oscillator sensor 26; and a liquid supply portion, which is composed of a first hose 29a connected to the supply channel 40a and a second hose 29b connected to the discharge channel 40b.

[0153] The target chemical solution is supplied through the first hose 29a and supply channel 40a to the region 44 formed by the quartz crystal oscillator sensor 26, the seal 42, and the block 40. Specifically, the seal 42 is disposed outside the region 44. This allows the target chemical solution to contact the adsorption layer 34 on the surface 30a of the electrode 30 of the quartz crystal oscillator 27 of the quartz crystal oscillator sensor 26. The target chemical solution is then discharged from the region 44 through the discharge channel 40b and the second hose 29b. The first hose 29a and discharge channel 40b, and the second hose 29b and discharge channel 40b, constitute a circulation line.

[0154] The movement of the target drug solution in the first hose 29a and the supply channel 40a and the second hose 29b and the discharge channel 40b is performed by the supply unit 20 (see FIG. Figure 1 ) to carry out.

[0155] For example, the sealing portion 42 and the sealing portion 43 are of the same size and are formed of, for example, O-rings. The target chemical solution is not supplied to the region 45 surrounded by the quartz crystal oscillator sensor 26 , the sealing portion 43 , and the temperature regulating portion 28 .

[0156] Furthermore, in the flow cell unit 12 , it is preferable to form at least a portion of the liquid contact portion that contacts the target drug solution from a fluorine-based resin because this can suppress elution into the target drug solution and suppress a decrease in purity measurement accuracy.

[0157] In the measuring device 10, the surface of the following region 44 corresponds to a part of the liquid contact portion that contacts the target liquid, and the region 44 is formed by being surrounded by the above-mentioned quartz crystal oscillator sensor 26, the sealing portion 42 and the block 40 and holding the target liquid on the quartz crystal oscillator sensor 26. In addition to the region 44, in the supply portion that brings the target liquid into contact with the quartz crystal oscillator sensor 26, the portion in contact with the target liquid in the liquid supply portion that supplies the target liquid to the quartz crystal oscillator sensor is also a liquid contact portion. It is preferred that at least a part of these liquid contact portions be composed of a fluororesin. That is, in the measuring device for sensing impurities in a liquid containing an organic solvent (the above-mentioned measuring device having a quartz crystal oscillator sensor), at least a part of the liquid contact portion that contacts the target liquid is preferably composed of a fluororesin. In addition, as the above-mentioned liquid contact portion, it is preferred that it be a liquid contact portion other than the adsorption layer and the quartz crystal oscillator. Examples of the liquid supply unit include a supply line that supplies liquid in one direction and a circulation line that circulates a target chemical solution and supplies it to a quartz crystal oscillator sensor.

[0158] More specifically, in Figure 4 In the embodiment, the liquid contact portions are the surface 40c of the block 40 of the flow cell unit 12 that contacts the region 44, the surface 42a of the sealing portion 42 that contacts the region 44 and retains the target liquid disposed on the quartz crystal oscillator sensor 26 in the region 44, the supply channel 40a of the block 40, and the discharge channel 40b of the block 40. Furthermore, the interior of the first hose 29a and the interior of the second hose 29b also serve as liquid contact portions that contact the target liquid. The portions of the first hose 29a and the second hose 29b that contact the target liquid are preferably made of a fluorine-based resin.

[0159] Among them, at least a portion of the liquid contact portion contacting the target drug solution of the sealing portion 42 , the liquid contact portion contacting the target drug solution of the block 40 , and the liquid contact portion contacting the target drug solution of the liquid feeding portion is preferably formed of a fluorine-based resin.

[0160] The fluorine-based resin may be any resin containing fluorine atoms.

[0161] Fluorine-based resins are not particularly limited as long as they are resins (polymers) containing fluorine atoms, and known fluorine-based resins can be used. Examples of fluorine-based resins include polytetrafluoroethylene (PTFE, tensile strength: 20-35 MPa, Shore D hardness: 50-55), perfluoroalkoxyalkanes, polychlorotrifluoroethylene, polyvinylidene fluoride, ethylene tetrafluoroethylene copolymers, ethylene chlorotrifluoroethylene copolymers, perfluoroethylene propylene copolymers, tetrafluoroethylene perfluoroalkyl vinyl ether copolymers, and cyclopolymers of perfluoro(butylene vinyl ether) (CYTOP (registered trademark)).

[0162] When the liquid contact portion of the flow cell unit 12 (the portion in contact with the target liquid) of the block 40 is made of a fluororesin, the fluororesin preferably has a tensile strength of 20 to 60 MPa and a Shore D hardness of 60 to 80.

[0163] The fluororesin constituting the liquid contact portion in contact with the target liquid of the block 40 is preferably perfluoroalkoxyalkane (PFA, tensile strength: 25-35 MPa, Shore D hardness: 62-66), ethylene tetrafluoroethylene copolymer (ETFE, tensile strength: 38-42 MPa, Shore D hardness: 67-78), perfluoroethylene propylene copolymer (FEP, tensile strength: 20-30 MPa, Shore D hardness: 60-65), polychlorotrifluoroethylene (PCTFE, tensile strength: 31-41 MPa, Shore D hardness: 75-80) or polyvinylidene fluoride (PVDF, tensile strength: 30-60 MPa, Shore D hardness: 64-79).

[0164] In addition, the tensile strength was measured according to JIS K 7161.

[0165] The Shore D hardness is measured in accordance with JIS K 7215.

[0166] Furthermore, the fluorine-based resin constituting the liquid contact portion (the portion in contact with the target liquid) that contacts the target liquid in the liquid delivery portion that delivers the target liquid to region 44 preferably has repeating units containing fluorine atoms, carbon atoms, and atoms other than fluorine atoms and carbon atoms (hereinafter also referred to as "specific repeating units"). Examples of these other atoms include hydrogen atoms and chlorine atoms. In other words, the specific repeating unit preferably contains fluorine atoms, carbon atoms, and at least one other atom selected from the group consisting of hydrogen atoms and chlorine atoms.

[0167] The fluorine-based resin constituting the portion of the liquid delivery section that contacts the target chemical solution is preferably a ternary copolymer of tetrafluoroethylene, hexafluoropropylene, and vinylidene fluoride (THV soft fluorine resin), polyvinylidene fluoride, ethylene tetrafluoroethylene copolymer, or polychlorotrifluoroethylene.

[0168] The methods for measuring tensile strength and Shore D hardness are as described above.

[0169] The portion of the sealing portion 42 that contacts the target chemical solution disposed on the quartz crystal oscillator sensor 26 in the region 44 (the surface 42 a that contacts the region 44 ) is preferably made of a fluorine-based resin.

[0170] The fluororesin forming the portion of the sealing portion 42 that contacts the target drug solution preferably has a tensile strength of 20 to 40 MPa. The fluororesin forming the portion of the sealing portion 42 that contacts the target drug solution preferably has a Shore D hardness of 56 to 70. Furthermore, the flexural modulus of the fluororesin forming the portion of the sealing portion 42 that contacts the target drug solution preferably has a flexural modulus of 0.5 to 3 GPa.

[0171] When the fluorine-based resin constituting the portion of the sealing portion 42 that contacts the target drug solution satisfies the aforementioned tensile strength, Shore D hardness, and flexural modulus, more stable measurement can be performed without inhibiting the vibration of the quartz crystal oscillator sensor 26 .

[0172] The methods for measuring tensile strength and Shore D hardness are as described above.

[0173] The flexural modulus is measured in accordance with JIS K 7171.

[0174] The fluorine-based resin constituting the portion of the sealing portion 42 that contacts the target drug solution is preferably perfluoroalkoxyalkane, perfluoroethylene-propylene copolymer, ethylene-chlorotrifluoroethylene copolymer, ethylene-tetrafluoroethylene copolymer, polychlorotrifluoroethylene, or polyvinylidene fluoride.

[0175] The supply unit 20 circulates the target drug solution using the first tube 29a and the second tube 29b, but the present invention is not limited thereto and may be configured to flow the target drug solution in one direction.

[0176] When the target chemical solution is circulated and supplied to the quartz crystal oscillator 27 , the circulation flow rate of the target chemical solution is preferably 0.01 to 1000 ml / s. A circulation flow rate of 0.01 to 1000 ml / s allows a sufficient amount of impurities required for detection to adhere to the surface of the adsorption layer 34 .

[0177] If the amount of impurities increased when the target chemical solution is circulated for 1 hour is 1000 ppt by mass or less, the accuracy of purity measurement will not be reduced, which is preferable.

[0178] The arrangement of the quartz crystal oscillator sensor 26 in the flow cell unit 12 is not particularly limited.

[0179] [Management methods]

[0180] Next, a description will be given of a method for managing the purity of a chemical solution by sensing impurities in the chemical solution containing an organic solvent.

[0181] The management method includes: step 1 of preparing a target medicinal solution containing an organic solvent; step 2 of bringing a quartz crystal oscillator sensor (in a measuring device for sensing impurities in a medicinal solution containing an organic solvent) containing an adsorption layer for adsorbing impurities and a quartz crystal oscillator into contact with the target medicinal solution to obtain a change in the resonant frequency of the quartz crystal oscillator caused by contact with the target medicinal solution; and step 3 of managing the purity of the medicinal solution by comparing whether the obtained change in the resonant frequency is within an allowable range of the change in the resonant frequency based on a predetermined purity of the target medicinal solution.

[0182] As shown in the above-described measuring device 10 , in step 2 , at least a portion of the liquid contact portion of the measuring device 10 that comes into contact with the target drug solution is made of a fluorine-based resin.

[0183] In the management method, similar to the aforementioned measuring device, the target drug solution is fed to the quartz crystal oscillator sensor so that the target drug solution contacts the quartz crystal oscillator sensor. By flowing the target drug solution in a single direction, the target drug solution can adhere to the quartz crystal oscillator sensor. Furthermore, the target drug solution can be circulated to the quartz crystal oscillator, with the circulation flow rate set at 0.01 to 1000 ml / s.

[0184] Below, the above Figure 1 The management method will be described in more detail using the measurement device 10 shown as an example. In the management method, for example, a target drug solution is circulated and supplied.

[0185] As described above, a target drug solution containing an organic solvent whose purity is controlled is prepared (step 1), and the target drug solution is stored in the supply unit 20 of the measuring device 10. The target drug solution contains impurities.

[0186] Next, the following process is repeated: the target chemical solution is supplied from the supply unit 20 toward the flow cell unit 12 through the first hose 29a and the supply channel 40a of the block 40 to the area 44, then returned to the supply unit 20 through the discharge channel 40b of the block 40 and the second hose 29b, and then supplied to the area 44 again through the first hose 29a and the supply channel 40a of the block 40. In this way, the target chemical solution is circulated and supplied to the quartz crystal oscillator 27, and contacts the adsorption layer 34 of the quartz crystal oscillator 27.

[0187] A high-frequency sinusoidal signal is applied from oscillator 14 to quartz crystal oscillator sensor 26 as a frequency signal. Prior to supplying the target medicinal solution, quartz crystal oscillator 27 is pre-vibrated at a resonant frequency, and the resonant frequency before supplying the target medicinal solution is obtained by detection unit 15. Then, for example, after the target medicinal solution has been supplied to quartz crystal oscillator 27 for a predetermined period of time, the resonant frequency is obtained by detection unit 15, and the change in the resonant frequency is then obtained (step 2). In other words, by implementing the method for measuring the medicinal solution in steps 1 and 2, the change in the resonant frequency can be obtained. The change in the resonant frequency obtained by detection unit 15 is output to calculation unit 16 and stored therein.

[0188] The calculation unit 16 reads the allowable range of change in the resonant frequency based on the purity of the target medicinal solution, which is preset and stored in the memory 18. The calculation unit 16 compares the allowable range of change in the resonant frequency stored in the memory 18 with the change in the resonant frequency obtained by the detection unit 15 to manage the purity of the medicinal solution (step 3). For example, if the comparison shows that the resonant frequency is within the allowable range, the display unit 23 indicates that the purity of the medicinal solution is within the allowable range. On the other hand, if the resonant frequency is outside the allowable range, the display unit 23 indicates that the purity of the medicinal solution is outside the allowable range.

[0189] In the management method, the purity of the drug solution can be easily obtained, and the purity of the target drug solution can be managed based on the obtained purity, thereby managing the quality of the drug solution.

[0190] The change amount of the resonance frequency and its allowable range stored in the memory 18 can be adjusted according to the above-mentioned Figure 3 The calibration curve L shown is obtained.

[0191] The above-mentioned management method is preferably implemented in a clean room. More specifically, it is preferably implemented in a clean room that meets the cleanliness level of Class 2 or higher specified in the international standard ISO 14644-1:2015 defined by the International Organization for Standardization.

[0192] [Other examples of quartz crystal oscillator sensors]

[0193] Figure 5 is a schematic diagram showing a second example of a quartz crystal oscillator sensor according to an embodiment of the present invention. Figure 6 This is a schematic cross-sectional view showing a second example of the quartz crystal oscillator sensor according to the embodiment of the present invention. Figure 7 1 is a schematic diagram showing a third example of a quartz crystal bulk oscillator sensor according to an embodiment of the present invention. Figure 8 : is a schematic cross-sectional view showing a third example of a quartz crystal oscillator sensor according to an embodiment of the present invention. Figures 4 to 8 In the quartz crystal oscillator sensor 26 shown, Figure 2 The same components of the quartz crystal oscillator sensor 26 are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0194] Figure 2 The quartz crystal oscillator sensor 26 shown in FIG. 1 is a structure in which one electrode 30 is provided on the surface 27a of the quartz crystal oscillator 27, but the structure is not limited thereto. Figure 5 and Figure 6 As shown, a first electrode 50 and a second electrode 51 may be provided on the surface 27a of the quartz crystal oscillator 27. The first electrode 50 and the second electrode 51 are formed, for example, of rectangular conductive layers and are arranged parallel to each other with a gap therebetween. The first electrode 50 and the second electrode 51 are electrically insulated from each other. The first adsorption layer 35 is provided on the surface 50a of the first electrode 50, and the second adsorption layer 36 is provided on the surface 51a of the second electrode 51.

[0195] The first electrode 50 and the electrode 31 are electrically connected to the first oscillating element 14a. The second electrode 51 and the electrode 31 are electrically connected to the second oscillating element 14b. The first oscillating element 14a and the second oscillating element 14b are provided in the oscillating unit 14 and are capable of independently applying a sinusoidal high-frequency signal as a frequency signal to the first electrode 50 and the electrode 31 and the second electrode 51 and the electrode 31, thereby causing the quartz crystal oscillator 27 to vibrate at a resonant frequency.

[0196] Furthermore, the first oscillator 14a and the second oscillator 14b are each electrically connected to the detection unit 15. The detection unit 15 includes a switch unit (not shown) that switches the connection between the first oscillator 14a and the second oscillator 14b. The switch unit alternately reads the frequency signal of the first oscillator 14a and the frequency signal of the second oscillator 14b into the detection unit 15. This allows the detection unit 15 to independently detect the resonant frequency of the first electrode 50 and the resonant frequency of the second electrode 51.

[0197] The first adsorption layer 35 on the surface 50a of the first electrode 50 and the second adsorption layer 36 on the surface 51a of the second electrode 51 can be the same or different. If the first adsorption layer 35 and the second adsorption layer 36 are different, the purity can be easily estimated by utilizing the difference in the resonant frequency of the first electrode 50 and the second electrode 51 and determining whether the difference is within a predetermined allowable range of change in the resonant frequency based on the purity of the target drug solution. This makes it easier to determine the purity of the drug solution, facilitating purity management and enabling easier management of the drug solution's quality. Preferably, at least one of the first adsorption layer 35 and the second adsorption layer 36 is an Au layer. By using an Au layer, one of the first electrode 50 and the second electrode 51 can be used as a reference electrode.

[0198] And, as Figure 7 and Figure 8 As shown, an electrode 52 may be provided on the surface 27a of the quartz crystal oscillator 27. The electrode 52 includes a first electrode portion 52a, a second electrode portion 52b, and a connecting portion 52c that connects the first and second electrode portions 52a and 52b at one end. The first and second electrode portions 52a and 52b are, for example, formed of rectangular conductive layers and arranged parallel to each other with a gap therebetween. The first and second electrode portions 52a and 52b are electrically connected. An adsorption layer 34 is provided on the electrode 52.

[0199] The first electrode portion 52a and the electrode 31 are electrically connected to the first oscillating element 14a. The second electrode portion 52b and the electrode 31 are electrically connected to the second oscillating element 14b. The first oscillating element 14a and the second oscillating element 14b are provided in the oscillating portion 14 and are capable of independently applying a sinusoidal high-frequency signal as a frequency signal to the first electrode 50 and the electrode 31 and the second electrode 51 and the electrode 31, thereby causing the quartz crystal oscillator 27 to vibrate at a resonant frequency.

[0200] Furthermore, the first oscillator 14a and the second oscillator 14b are each electrically connected to the detection unit 15. The detection unit 15 includes a switch unit (not shown) that switches the connection between the first oscillator 14a and the second oscillator 14b. The switch unit alternately reads the frequency signal of the first oscillator 14a and the frequency signal of the second oscillator 14b into the detection unit 15. As a result, the detection unit 15 can independently obtain the resonant frequency of the first electrode portion 52a and the resonant frequency of the second electrode portion 52b.

[0201] exist Figure 8 In the quartz crystal oscillator sensor 26 shown, an adsorption layer 34 is also provided on the first electrode portion 52a and the second electrode portion 52b, and the adsorption layer 34 can be different in the first electrode portion 52a and the second electrode portion 52b. In different cases, the purity can be easily inferred by utilizing the difference in the resonant frequency of the first electrode portion 52a and the second electrode portion 52b. As a result, the purity of the liquid medicine can be more easily obtained, the management of the purity becomes easy, and the quality of the liquid medicine can be easily managed. It is preferred to form an Au layer on at least one of the first electrode portion 52a and the second electrode portion 52b. By forming the Au layer, one of the first electrode portion 52a and the second electrode portion 52b can be used as a reference electrode.

[0202] [Kit]

[0203] As a method of indicating the quality of a drug solution, the purity measured by the measuring device 10 and the drug solution are displayed in association with each other, thereby making it possible to easily manage the quality of the drug solution. The association of such a drug solution and its purity is called a kit.

[0204] The kit includes a medical solution and an information display unit that displays or stores resonant frequency information of the medical solution. The medical solution is brought into contact with a quartz crystal oscillator sensor comprising an adsorption layer that absorbs impurities in the medical solution and a quartz crystal oscillator. The change in resonant frequency of the quartz crystal oscillator is determined, and the obtained change in resonant frequency is compared with a predetermined change in resonant frequency based on the purity of the medical solution. An evaluation of the purity of the medical solution relative to the obtained change in resonant frequency is then provided. Based on the evaluation, the obtained change in resonant frequency is associated with the purity of the medical solution and recorded as resonant frequency information of the medical solution. This resonant frequency information of the medical solution is then used to obtain information on the purity of the medical solution. The purity of the medical solution can be obtained using the resonant frequency information of the medical solution.

[0205] The above evaluation is performed by measuring the purity of the drug solution using the above-mentioned measuring device 10 .

[0206] The kit will be described in more detail below. Figure 9 is a schematic perspective view showing an example of a kit according to an embodiment of the present invention. Figure 10 This is a schematic diagram showing an example of the information display unit of the kit according to the embodiment of the present invention.

[0207] like Figure 9 As shown, the kit 60 includes, for example, a container 64 storing a medical solution 62 within an interior 64a. The container 64 is, for example, cylindrical, and has an information display 66 provided on a side surface 64b. Alternatively, the information display 66 may be provided on an upper surface 64c. The information display 66 displays or stores information on the resonant frequency of the medical solution.

[0208] As the information display unit 66, for example Figure 10 As shown, the resonance frequency information of the liquid medicine is represented by characters. However, the present invention is not limited thereto, and the resonance frequency information of the liquid medicine can be displayed on the information display unit 66 using at least one of characters, symbols, and barcodes. The barcode is not particularly limited, and a two-dimensional code may also be used.

[0209] The information display unit 66 is not limited to the following. Figure 10 The character-based display shown may also be an information recording medium such as an IC (integrated circuit) tag. In the case of an IC tag, the resonant frequency information of the medical solution can be read contactlessly using an IC tag reader. By using a barcode or IC tag as information display unit 66, for example, a reader can be used to monitor the quality of the medical solution.

[0210] The information display unit 66 that displays the resonance frequency information of the medical solution via the output unit 24 can be obtained via the output unit 24 of the measurement device 10 .

[0211] The management method, measurement method, measurement device, quartz crystal oscillator sensor, and kit of the present invention are basically configured as described above. While the management method, measurement method, measurement device, quartz crystal oscillator sensor, and kit of the present invention have been described in detail above, the present invention is not limited to the aforementioned embodiments and, of course, various improvements and modifications are possible without departing from the spirit of the present invention.

[0212] The target drug solution used in the present invention (hereinafter, also simply referred to as "drug solution") contains an organic solvent.

[0213] In this specification, an organic solvent refers to a liquid organic compound containing each component at a content of more than 10,000 ppm by mass relative to the total mass of the above-mentioned chemical solution. In other words, in this specification, a liquid organic compound containing more than 10,000 ppm by mass relative to the total mass of the above-mentioned chemical solution is equivalent to an organic solvent.

[0214] In this specification, the term "liquid" means liquid at 25°C and atmospheric pressure.

[0215] The content of the organic solvent in the drug solution is not particularly limited, but is preferably 98.0% by mass or more, more preferably greater than 99.0% by mass, further preferably greater than 99.90% by mass, and particularly preferably greater than 99.95% by mass, relative to the total mass of the drug solution. The upper limit is less than 100% by mass.

[0216] The organic solvent may be used alone or in combination of two or more. When two or more organic solvents are used, the total content is preferably within the above range.

[0217] The type of organic solvent is not particularly limited, and known organic solvents can be used. Examples of the organic solvent include alkylene glycol monoalkyl ether carboxylates, alkylene glycol monoalkyl ethers, alkyl lactates, alkyl alkoxypropionates, cyclic lactones (preferably having 4 to 10 carbon atoms), monoketone compounds (preferably having 4 to 10 carbon atoms) which may also have a ring, alkylene carbonates, alkyl alkoxyacetates, alkyl pyruvates, dialkyl sulfoxides, cyclic sulfonic acids, dialkyl ethers, monohydric alcohols, diols, alkyl acetates, and N-alkylpyrrolidone.

[0218] The organic solvent is preferably one or more selected from the group consisting of, for example, propylene glycol monomethyl ether acetate (PGMEA), propylene glycol monomethyl ether (PGME), cyclohexanone (CHN), ethyl lactate (EL), propylene carbonate (PC), isopropyl alcohol (IPA), 4-methyl-2-pentanol (MIBC), butyl acetate (nBA), propylene glycol monoethyl ether, propylene glycol monopropyl ether, methyl methoxypropionate, cyclopentanone, γ-butyrolactone, diisoamyl ether, isoamyl acetate, dimethyl sulfoxide, N-methylpyrrolidone, diethylene glycol, ethylene glycol, dipropylene glycol, propylene glycol, ethylene carbonate, sulfolane, cycloheptanone and 2-heptanone.

[0219] Examples of the use of two or more organic solvents include the simultaneous use of PGMEA and PGME and the simultaneous use of PGMEA and PC.

[0220] In addition, the type and content of the organic solvent in the chemical solution can be measured using a gas chromatograph.

[0221] The chemical solution may contain impurities in addition to the organic solvent. As described above, the impurities are adsorbed on the adsorption layer, thereby changing the resonance frequency.

[0222] Examples of impurities include metallic impurities and organic impurities.

[0223] Metal impurities refer to metal impurities contained in the chemical solution as metal ions and solids (such as metal elements and compounds containing particulate metals).

[0224] The types of metals contained in the metal impurities are not particularly limited, and examples thereof include Na (sodium), K (potassium), Ca (calcium), Fe (iron), Cu (copper), Mg (magnesium), Mn (manganese), Li (lithium), Al (aluminum), Cr (chromium), Si (nickel), Ti (titanium) and Zn (zirconium).

[0225] The metal impurities may be components inevitably contained in the components (raw materials) contained in the chemical solution, components inevitably contained during the production, storage and / or transfer of the chemical solution, or may be intentionally added.

[0226] When the chemical solution contains metal impurities, the content thereof is not particularly limited, and can be 0.01 to 500 ppt by mass relative to the total mass of the chemical solution.

[0227] As used herein, organic impurities are compounds different from the organic solvent that is the main component of a chemical solution, and are organic substances present at a concentration of 10,000 ppm by mass or less relative to the total mass of the chemical solution. Specifically, as used herein, organic substances present at a concentration of 10,000 ppm by mass or less relative to the total mass of the chemical solution are considered organic impurities, not organic solvents.

[0228] When organic impurities composed of a plurality of compounds are contained in the chemical solution, each compound corresponds to an organic impurity if it corresponds to an organic substance contained in a content of 10,000 ppm by mass or less as described above.

[0229] In addition, water is not included in the organic impurities.

[0230] Organic impurities may be added to the drug solution or may be inevitably mixed into the drug solution during the drug solution manufacturing process. Examples of cases where organic impurities are inevitably mixed into the drug solution during the drug solution manufacturing process include, but are not limited to, cases where organic impurities are contained in the raw materials used to manufacture the drug solution (e.g., organic solvents) and cases where organic impurities are mixed into the drug solution during the drug solution manufacturing process (e.g., contaminants).

[0231] The total content of the organic impurities in the above-mentioned chemical solution is not particularly limited, but can be 0.1 to 5000 ppm by mass relative to the total mass of the chemical solution.

[0232] The organic impurities may be used alone or in combination of two or more. When two or more organic impurities are used in combination, the total content is preferably within the above range.

[0233] Examples of organic impurities include butylated hydroxytoluene (BHT), distearyl thiodipropionate (DSTP), 4,4'-butylenebis-(6-tert-butyl-3-methylphenol), 2,2'-methylenebis-(4-ethyl-6-tert-butylphenol), and antioxidants such as those described in Japanese Patent Application Publication No. 2015-200775; unreacted raw materials; structural isomers and by-products produced when producing organic solvents; eluted substances from components of an organic solvent production device (for example, plasticizers eluted from rubber components such as O-rings); and the like.

[0234] The chemical solution may contain water. The type of water is not particularly limited, and for example, distilled water, ion-exchanged water, and pure water can be used.

[0235] Water may be added to the chemical solution or may be inevitably mixed into the chemical solution during the chemical solution manufacturing process. Examples of unavoidable mixing during the chemical solution manufacturing process include cases where water is contained in raw materials (e.g., organic solvents) used in the chemical solution manufacturing process and cases where water is mixed into the chemical solution during the chemical solution manufacturing process (e.g., as a contaminant).

[0236] The water content in the drug solution is not particularly limited, but is generally preferably 2.0% by mass or less, more preferably 1.0% by mass or less, and even more preferably less than 0.5% by mass, relative to the total mass of the drug solution.

[0237] When the water content in the chemical solution is 1.0 mass % or less, the production yield of semiconductor chips is further improved.

[0238] The lower limit is not particularly limited, but is often about 0.01% by mass. In production, it is difficult to reduce the water content to below the above range.

[0239] The method for preparing the above-mentioned chemical solution is not particularly limited. For example, methods such as purchasing an organic solvent and reacting the raw materials to obtain the organic solvent can be used. Furthermore, it is preferable to prepare a chemical solution having a low impurity content as described above (for example, a chemical solution having an organic solvent content of 99% by mass or greater). Commercially available products of this type of organic solvent include, for example, "high-purity grade products."

[0240] Furthermore, the drug solution may be subjected to purification treatment as needed.

[0241] Examples of the purification method include distillation and filtration.

[0242] Example

[0243] Hereinafter, the present invention will be further described in detail based on the examples. The materials, usage amounts, ratios, processing contents and processing sequences shown in the following examples can be appropriately changed without departing from the gist of the present invention. Therefore, the scope of the present invention should not be interpreted as being limited by the examples shown below.

[0244] <Example A>

[0245] [Manufacturing of liquid medicine]

[0246] First, the chemical solutions used in the examples described below were prepared. Specifically, a high-purity organic solvent reagent with a purity of 99% by mass or greater was purchased. The purchased reagent was then filtered using an appropriate combination of the following filters to prepare chemical solutions with varying levels of impurities (A1-A20, B1-B7, C1-C5, D1-D5, and E1-E7).

[0247] IEX-PTFE (15nm): 15nm IEX PTFE manufactured by Entegris, Inc.

[0248] PTFE (12nm): 12nm PTFE manufactured by Entegris, Inc.

[0249] UPE (3nm): 3nm PE filter manufactured by Entegris, Inc.

[0250] In order to adjust the amount of impurities in the chemical solution described later, the purchase location of the organic solvent reagent may be appropriately changed, the purity level may be changed, or a distillation treatment may be performed before the above-mentioned filtration treatment.

[0251] [Evaluation of a Quartz Crystal Oscillator Sensor (Part 1)]

[0252] A quartz crystal oscillator sensor having a Si layer formed as an adsorption layer on the electrode portion was prepared (reference Figure 2 ), the quartz crystal oscillator sensor was immersed in the chemical solution shown in Table 1 below for 60 minutes, and the final change in the resonant frequency of the quartz crystal oscillator (Hz) was calculated. The resonant frequency of the quartz crystal oscillator before immersion in the chemical solution was 27 MHz.

[0253] The results are summarized in Table 1.

[0254] [Evaluation using surface inspection equipment (Part 1)]

[0255] First, a silicon wafer with a diameter of approximately 300 mm (12 inches) was prepared.

[0256] Next, using a surface inspection apparatus (SP-5; manufactured by KLA Tencor), the number of defects present on the silicon wafer was measured (this was set as an initial value).

[0257] Next, each chemical solution was spin-coated on a silicon wafer at 1500 rpm using "CLEAN TRACK LITHIUS (product name)" manufactured by Tokyo Electron Limited, and then the silicon wafer was spin-dried.

[0258] Next, using the surface inspection device described above, the number of defects present on the silicon wafer after the chemical solution was applied was measured (this is referred to as the measured value). The difference between the initial value and the measured value (measured value - initial value) was calculated and used as the defect count. This defect count represents the amount of impurities in the chemical solution remaining on the silicon wafer; a smaller value indicates a lower amount of impurities in the chemical solution.

[0259] The results are summarized in Table 1.

[0260] The evaluation was performed in a clean room satisfying cleanliness level 2 or higher as defined in the international standard ISO 14644-1:2015 defined by the International Organization for Standardization.

[0261] In Table 1, the "Chemical Solution" column shows the chemical solution used in each example. For example, in Example 1, chemical solutions A1 to A20 containing nBA (butyl acetate) were used, and the amounts of impurities in chemical solutions A1 to A20 varied.

[0262] The symbols of the chemical solutions in Table 1 represent the following chemical solutions.

[0263] nBA: butyl acetate

[0264] MIBC: 4-methyl-2-pentanol

[0265] PGMEA: Propylene glycol monomethyl ether acetate

[0266] IPA: Isopropyl alcohol

[0267] CHN: Cyclohexanone

[0268] [Table 1]

[0269]

[0270] As shown in Table 1, the amount of change in the resonance frequency and the number of defects are correlated, and the number of defects tends to increase when the amount of change in the resonance frequency is larger.

[0271] And, as Figure 3 As shown, the change in resonance frequency (quartz crystal oscillator sensor evaluation (resonance frequency change (Hz))) and the number of defects (surface inspection device evaluation (number of defects)) for all the chemical solutions of Examples 1 to 5 were plotted on a rectangular coordinate system with the change in resonance frequency as the horizontal axis and the number of defects as the vertical axis. A calibration curve passing through the plotted points was prepared by the least squares method, and the coefficient of determination (R 2 ), the result is calculated to be 0.8004 (reference Figure 11 ). The closer the coefficient of determination is to 1.000, the more consistent the result is. However, the results in Table 1 show that the correlation between the change in the resonance frequency and the number of defects is high.

[0272] In addition, when implementing [Evaluation using a quartz crystal oscillator sensor (Part 1)], the evaluation was carried out in a clean room that meets the cleanliness level 2 or above defined by the international standard ISO14644-1:2015 defined by the International Organization for Standardization, and the temperature of the chemical solution was adjusted to 23°C. In addition, the change in resonant frequency was measured in the same order as in Examples 1 to 5 above.

[0273] Table 2 shows the obtained results of the amount of change in the resonance frequency and the [Evaluation using the surface inspection device] obtained above.

[0274] [Table 2]

[0275]

[0276] The points of the change in resonance frequency (quartz crystal oscillator sensor evaluation (resonance frequency change (Hz))) and the number of defects (surface inspection device evaluation (number of defects)) for all the chemical solutions of Examples 6 to 10 were plotted on a rectangular coordinate system with the change in resonance frequency as the horizontal axis and the number of defects as the vertical axis. A calibration curve passing through the plotted points was prepared using the least squares method, and the coefficient of determination (R 2), the result is calculated to be 0.9626. The results in Table 2 are better than those in Table 1.

[0277] <Example B>

[0278] The chemical solutions used in each example (A21-A40, B8-B14, C6-C10, D6-D10, and E8-E14) were prepared in the same order as in Example A. The amount of impurities in each chemical solution varied. The concentration of impurities in the chemical solution was determined by LC / MS by integrating the peak values ​​of all components in the main chemical solution, excluding the chemical solution, and converting the peak values ​​to n-hexane.

[0279] [Evaluation of a Quartz Crystal Oscillator Sensor (Part 2)]

[0280] Prepare Figure 2 The adsorption layers shown are the quartz crystal oscillator sensors of the layers shown in Table 3 (Si layer, SiO2 layer, SiOC layer, Cu layer, Co layer, Ti layer, W layer, TiN layer, Ta layer, TaN layer), and the like. Figure 4 The flow cell unit of the measuring device shown in FIG Figure 1 ), each chemical solution (A21-A40, B8-B14, C6-C10, D6-D10, E8-E14) was brought into contact with a quartz crystal oscillator sensor, and the change in the resonant frequency of the quartz crystal oscillator was evaluated. Specifically, the temperature control unit maintained the chemical solution temperature at 23°C, and the change in the resonant frequency (Hz) of the quartz crystal oscillator was measured when each chemical solution was circulated through the flow cell unit at a circulation flow rate of 20 ml / s for 60 minutes. The resonant frequency of the quartz crystal oscillator before contact with the chemical solution was 27 MHz.

[0281] The results are summarized in Tables 3 to 7.

[0282] The evaluation was performed in a clean room satisfying cleanliness level 2 or higher as defined in the international standard ISO 14644-1:2015 defined by the International Organization for Standardization.

[0283] Furthermore, the liquid contact parts of each component of the flow cell unit in the above-mentioned resonance frequency measuring device (the liquid contact part of the block, the liquid contact part of the sealing part, and the liquid contact part of the liquid supply part) are made of the same fluorine-based resin as in Example 24 described later.

[0284] [Evaluation using surface inspection equipment (Part 2)]

[0285] First, various substrates (Si substrate, SiO2 substrate, SiOC substrate, Cu substrate, Co substrate, Ti substrate, W substrate, TiN substrate, Ta substrate, TaN substrate) were prepared.

[0286] Next, using a wafer surface inspection apparatus (SP-5; manufactured by KLA Tencor), the number of defects present on each substrate was measured (this was set as an initial value).

[0287] Next, using "CLEAN TRACK LITHIUS (product name)" manufactured by Tokyo Flectron Limited, each chemical solution (A21 to A40, B8 to B14, C6 to C10, D6 to D10, and E8 to E14) was spin-coated on the substrate at 1500 rpm, and then the substrate was spin-dried.

[0288] Next, the number of defects present on the substrate after the chemical solution application was measured using the above-mentioned apparatus (SP-5) (this was referred to as the measured value). Next, the difference between the initial value and the measured value (measured value - initial value) was calculated and referred to as the number of defects.

[0289] The results are summarized in Tables 3 to 7.

[0290] The evaluation was performed in a clean room satisfying cleanliness level 2 or higher as defined in the international standard ISO 14644-1:2015 defined by the International Organization for Standardization.

[0291] Tables 3 to 7 show side-by-side the results for adsorption layers and substrates made of the same metal type. For example, the "Si" column in Table 3 shows the results of [Evaluation using a quartz crystal sensor (Part 2)] using a "Si layer" as the adsorption layer and [Evaluation using a surface inspection device (Part 2)] using a Si substrate.

[0292] [Table 3]

[0293]

[0294] [Table 4]

[0295]

[0296] [Table 5]

[0297]

[0298] [Table 6]

[0299]

[0300] [Table 7]

[0301]

[0302] As shown in the above table, when the adsorption layer and substrate are made of the same type of metal, the correlation between the change in resonance frequency and the number of defects is high, and the number of defects tends to increase when the change in resonance frequency is large.

[0303] <Example C>

[0304] The change in resonance frequency was measured by the same procedure as in [Evaluation using a quartz crystal oscillator sensor (Part 2)] except that an Au layer was used instead of the Si layer.

[0305] Next, the difference was calculated by subtracting the change in the resonance frequency obtained by using the Au layer from the change in the resonance frequency obtained by using the Si layer.

[0306] The results are shown in Table 8.

[0307] In Table 8, the "Si layer - Au layer" column indicates the difference obtained by subtracting the "Quartz crystal oscillator sensor evaluation (resonance frequency change (Hz))" in the "Au layer" column from the "Quartz crystal oscillator sensor evaluation (resonance frequency change (Hz))" in the "Si layer" column.

[0308] [Table 8]

[0309]

[0310] The points of the change in resonance frequency (quartz crystal oscillator sensor evaluation (resonance frequency change (Hz))) and the number of defects (surface inspection device evaluation (number of defects)) for the "Si layer" column of Examples 16 to 20 were plotted on a rectangular coordinate system with the change in resonance frequency as the horizontal axis and the number of defects as the vertical axis. A calibration curve passing through the plotted points was prepared by the least squares method, and the coefficient of determination (R 2 ), which is calculated to be 0.9915.

[0311] Furthermore, the differences in the changes in the resonant frequencies of the "Si layer - Au layer" columns of Examples 16 to 20 and the number of defects in the "Si layer" column (surface inspection device evaluation (number of defects)) were plotted, and a calibration curve passing through the plotted points was prepared by the least squares method, and the coefficient of determination (R 2 ), which is calculated to be 0.996.

[0312] From the above results, it was confirmed that when the Au layer was used as a reference, the correlation between the change amount of the resonance frequency and the number of defects was higher.

[0313] <Example D>

[0314] The chemical solutions (A41 to A140) used in each example were prepared in the same procedure as in Example A above.

[0315] Prepare Figure 2 The adsorption layer shown is a quartz crystal oscillator sensor with a Si layer, and the quartz crystal oscillator sensor has the above-mentioned Figure 4 The flow cell unit of the measuring device shown in FIG Figure 1 ), the chemical solutions (A41 to A140) were brought into contact with a quartz crystal oscillator sensor, and the change in the resonant frequency of the quartz crystal oscillator was evaluated. Specifically, the temperature of the chemical solution was adjusted to 23°C using the temperature control unit. The change in the resonant frequency (Hz) of the quartz crystal oscillator was measured when each chemical solution was circulated through the flow cell unit at a circulation rate of 20 ml / s for 60 minutes. The resonant frequency of the quartz crystal oscillator before contact with the chemical solution was 27 MHz.

[0316] In addition, in the measuring device used, at least a portion of the liquid contact portion is made of a fluorine-based resin.

[0317] Specifically, in the flow cell unit Figure 4 When the liquid contact part (the part in contact with the target drug solution) of the block shown is composed of perfluoroethylene propylene copolymer (FEP, tensile strength: 20-30 MPa, Shore D hardness: 60-65, bending modulus: 0.55-0.67 GPa), the "circulation pool" column in Tables 9-10 is marked as "yes", and when it is not composed of fluorine-based resin, it is marked as "-".

[0318] In addition, when the liquid contact portion of the liquid delivery portion (the portion that contacts the target drug solution) is made of THV soft fluororesin, the "Liquid Delivery Portion" column in Tables 9 and 10 is marked as "Yes", and when it is not made of fluororesin, it is marked as "-".

[0319] And, in Figure 4 When the liquid contact portion (the portion that comes into contact with the target drug liquid) of the sealing portion that retains the target drug liquid in the area shown is composed of polyvinylidene fluoride (PVDF, tensile strength: 30 to 60 MPa, Shore D hardness: 64 to 79), the "Sealing portion A" column in Tables 9 to 10 is marked as "Yes", and when it is not composed of the above-mentioned fluorine-based resin, it is marked as "-".

[0320] In addition, Figure 4 When the liquid contact portion (the portion that comes into contact with the target drug liquid) of the sealing portion that retains the target drug liquid in the area shown is composed of perfluoroalkoxyalkane (PFA, tensile strength: 25 to 35 MPa, Shore D hardness: 62 to 66), the "Seal B" column in Tables 9 and 10 is marked as "Yes", and when the liquid contact portion of the above-mentioned sealing portion is not composed of a fluororesin, it is marked as "-".

[0321] Furthermore, when measuring the change in the resonant frequency, the amount of impurities eluted from the measuring device into the target drug solution was measured using LC / MS (Thermo LC / MS QE plus).

[0322] [Table 9]

[0323]

[0324] [Table 10]

[0325]

[0326] As shown in Tables 9 and 10 above, in Examples 21 to 24 in which at least a portion of the liquid-contacting portion of the measuring device that contacts the target liquid is made of a fluororesin, it was confirmed that the amount of impurities eluted from the measuring device was smaller than that in Example 25 in which no fluororesin was used. As a result, the correlation between the change in resonant frequency and the number of defects was higher.

[0327] The points of the change in resonance frequency (quartz crystal sensor evaluation (resonance frequency change (Hz))) and the number of defects (surface inspection device evaluation (number of defects)) for Example 21 were plotted on a rectangular coordinate system with the change in resonance frequency as the horizontal axis and the number of defects as the vertical axis. A calibration curve passing through the plotted points was prepared by the least squares method, and the coefficient of determination (R 2 ), the calculated result was 0.7318. The coefficients of determination were also calculated for Examples 22 to 25, and the results were 0.8086, 0.9843, 0.9936, and 0.3297, respectively. These results confirm that Examples 21 to 24, in which at least a portion of the liquid contact portion of the measuring device was composed of a fluorine-based resin, exhibited superior correlation compared to Example 25, in which the liquid contact portion of the measuring device was not composed of a fluorine-based resin.

[0328] In Example 23, the flow cell unit Figure 4 When the resin of the liquid contact portion (the portion in contact with the target chemical solution) of the block shown was changed from perfluoroethylene-propylene copolymer to perfluoroalkoxyalkane, ethylene-tetrafluoroethylene copolymer, perfluoroethylene-propylene copolymer, polychlorotrifluoroethylene, or polyvinylidene fluoride, correlation coefficients exceeding 0.95 were confirmed. However, these results were slightly inferior to the result of 23 (0.984).

[0329] Furthermore, in Example 23, when the resin constituting the liquid contact portion of the liquid delivery unit (the portion in contact with the target drug solution) was changed from THV soft fluororesin to polyvinylidene fluoride, ethylene tetrafluoroethylene copolymer, or polychlorotrifluoroethylene, correlations with coefficients exceeding 0.95 were observed. However, these results were slightly inferior to those in Example 23 (0.984).

[0330] And, in Example 23, Figure 4 When the resin constituting the liquid contact portion (the portion in contact with the target drug) of the seal that retains the target drug in the region shown above was changed from polyvinylidene fluoride to perfluoroethylene-propylene copolymer, ethylene-chlorotrifluoroethylene copolymer, ethylene-tetrafluoroethylene copolymer, or polychlorotrifluoroethylene, correlations with coefficients exceeding 0.95 were confirmed. However, these results were slightly inferior to the result of 23 (0.984).

[0331] Furthermore, in Example 23, the flow cell unit Figure 4 The resin of the liquid contact portion (the portion in contact with the target drug solution) of the block shown, the resin of the liquid contact portion (the portion in contact with the target drug solution) constituting the liquid delivery portion, and Figure 4 In the configuration shown above, when any of the resins in the liquid contact portion (the portion in contact with the target liquid) of the seal portion retaining the target liquid in the region was replaced with polytetrafluoroethylene, a correlation coefficient exceeding 0.85 and less than 0.95 was obtained. These results confirm that superior effects were achieved compared to when a fluorine-based resin other than polytetrafluoroethylene was used as the resin for the liquid contact portion.

[0332] In addition, in the flow cell unit Figure 4 The resin of the liquid contact portion (the portion in contact with the target drug solution) of the block shown, the resin of the liquid contact portion (the portion in contact with the target drug solution) constituting the liquid delivery portion, and Figure 4 When all the resins in the liquid contact portion (portion in contact with the target chemical liquid) of the sealing portion of the configuration for retaining the target chemical liquid in the region are polytetrafluoroethylene, the ratio 22 is excellent, but the correlation coefficient is 0.85 or less.

[0333] <Example E>

[0334] [Manufacturing of liquid medicine]

[0335] High-purity nBA of 99% by mass or higher was purchased and filtered using an appropriate combination of the following filters to prepare two chemical solutions (chemical solution X and chemical solution Y) with different impurity levels.

[0336] IEX-PTFE (15nm): 15nm IEX PTFE manufactured by Entegris, Inc.

[0337] PTFE (12nm): 12nm PTFE manufactured by Entegris, Inc.

[0338] UPE (3nm): 3nm PE filter manufactured by Entegris, Inc.

[0339] Next, in the above-mentioned <Example D>, the change in resonance frequency obtained by the results of Example 24 (quartz crystal oscillator sensor evaluation (change in resonance frequency (Hz))) and the number of defects (surface inspection device evaluation (number of defects)) is set as the rectangular coordinate data with the horizontal axis and the number of defects as the vertical axis, and the case where the change in resonance frequency is below 2000 Hz is set as the allowable range.

[0340] Next, using the chemical solution X and the chemical solution Y, the same procedure as in Example 24 was followed to determine the “quartz crystal oscillator sensor evaluation (resonance frequency change (Hz))”.

[0341] The previously set allowable range of resonant frequency variation (2000 Hz or less) is then stored in the memory of the measuring device. The calculation unit then determines whether the resonant frequency variation obtained using chemical solutions X and Y falls within this allowable range. The calculation results indicate that chemical solution X falls within the allowable range, while chemical solution Y falls outside of it.

[0342] Using these chemical solutions X and Y, the [Evaluation Using a Surface Inspection Device (Part 1)] performed in <Example A> was carried out. The results confirmed that chemical solution X had a low number of defects, approximately 20 or less, while chemical solution Y had a high number of defects, exceeding 20. These results also confirmed that the purity of the chemical solution can be managed by measuring the change in the resonant frequency of the chemical solution.

[0343] Explanation of symbols

[0344] 10- measuring device, 12- circulation cell unit, 14- oscillating part, 14a- 1st oscillating unit, 14b- 2nd oscillating unit, 15- detecting part, 16- calculating part, 20- supply part, 18- memory, 22- control part, 26- quartz crystal oscillator sensor, 27- quartz crystal oscillator, 27a- surface, 27b- back, 28- temperature control part, 29a- 1st hose, 29b- 2nd hose, 30- electrode, 30a- surface, 31- electrode Pole, 34-adsorption layer, 40-block, 40a-supply channel, 40b-discharge channel, 40c, 42a-surface, 42, 43-sealing part, 44-region, 45-region, 50-first electrode, 51-second electrode, 52-electrode, 52a-first electrode part, 52b-second electrode part, 52c-connecting part, 60-kit, 62-drug solution, 64-container, 64a-interior, 64b-side, 64c-top, 66-information display part.

Claims

1. A method for managing the purity of a liquid medicine containing an organic solvent by sensing impurities in the liquid medicine, the method comprising: Step 1: preparing a target drug solution containing an organic solvent; Step 2: bringing a quartz crystal oscillator sensor including an adsorption layer that adsorbs the impurities and a quartz crystal oscillator into contact with the target chemical solution, and obtaining a change in the resonance frequency of the quartz crystal oscillator caused by the contact between the adsorption layer and the target chemical solution; and Step 3: comparing the obtained change in the resonance frequency to see whether it is within a preset allowable range of the change in the resonance frequency based on the purity of the target medicinal solution, thereby managing the purity of the medicinal solution. In the step 2, at least a portion of the liquid contact portion that contacts the target drug solution is made of a fluorine-based resin. The resonance frequency of the quartz crystal oscillator changes depending on the amount of impurities adsorbed on the adsorption layer.

2. The management method according to claim 1, wherein: The target chemical solution is fed to the quartz crystal oscillator sensor so that the target chemical solution comes into contact with the quartz crystal oscillator sensor.

3. The management method according to claim 1 or 2, wherein: The target chemical liquid is caused to flow toward the quartz crystal oscillator sensor in a unidirectional manner, and the target chemical liquid is brought into contact with the quartz crystal oscillator sensor.

4. The management method according to claim 1 or 2, wherein: The target chemical solution is circulated and supplied to the quartz crystal oscillator sensor, and the circulation flow rate of the target chemical solution is 0.01 to 1000 ml / s.

5. The management method according to claim 1 or 2, wherein: The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

6. The management method according to claim 1 or 2, wherein: The quartz crystal oscillator sensor has a plurality of adsorption layers. The step 2 is a step of obtaining the change amount of the resonance frequency for each of the plurality of adsorption layers. Step 3 is a step of managing the purity of the target chemical solution by calculating differences in the amount of change in the resonance frequency of each of the plurality of adsorption layers and comparing the obtained values ​​to see whether they are within a preset allowable range of the amount of change in the resonance frequency based on the purity of the target chemical solution.

7. The management method according to claim 6, wherein: At least one of the plurality of adsorption layers is an Au layer.

8. A method for measuring a medicinal solution, comprising: Step 1, preparing a target drug solution containing an organic solvent; and Step 2: bringing a quartz crystal oscillator sensor including an adsorption layer for adsorbing impurities in the target chemical solution and a quartz crystal oscillator into contact with the target chemical solution, and obtaining a change in the resonant frequency of the quartz crystal oscillator caused by the contact between the adsorption layer and the target chemical solution. In the step 2, at least a portion of the liquid contact portion that contacts the target drug solution is made of a fluorine-based resin. The resonant frequency of the quartz crystal oscillator changes according to the amount of impurities adsorbed on the adsorption layer. The obtained change in the resonance frequency is used to manage the purity of the target medical fluid by comparing whether the change is within a preset allowable range of the change in the resonance frequency based on the purity of the target medical fluid.

9. The measuring method according to claim 8, wherein The target chemical solution is fed to the quartz crystal oscillator sensor so that the target chemical solution comes into contact with the quartz crystal oscillator sensor.

10. The measuring method according to claim 8 or 9, wherein The target chemical liquid is caused to flow toward the quartz crystal oscillator sensor in a unidirectional manner, and the target chemical liquid is brought into contact with the quartz crystal oscillator sensor.

11. The measuring method according to claim 8 or 9, wherein The target chemical solution is circulated and supplied to the quartz crystal oscillator sensor, and the circulation flow rate of the target chemical solution is 0.01 to 1000 ml / s.

12. The measuring method according to claim 8 or 9, wherein The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

13. The measuring method according to claim 8 or 9, wherein The quartz crystal oscillator sensor has a plurality of adsorption layers. The step 2 is a step of obtaining the amount of change in the resonance frequency for each of the plurality of adsorption layers.

14. The assay method according to claim 13, wherein At least one of the plurality of adsorption layers is an Au layer.

15. A measuring device for sensing impurities in a medical solution containing an organic solvent, the measuring device comprising: a quartz crystal oscillator sensor, contacting the target chemical solution containing the organic solvent and comprising an adsorption layer for adsorbing the impurities and a quartz crystal oscillator; an oscillating unit for vibrating the quartz crystal oscillator at a resonance frequency; a detection unit connected to the quartz crystal oscillator sensor and configured to detect a change in the resonance frequency of the quartz crystal oscillator caused by contact between the adsorption layer and the target chemical solution; and a supply unit that supplies the target chemical solution to the quartz crystal oscillator sensor so that the target chemical solution comes into contact with the quartz crystal oscillator sensor; At least a portion of the liquid contact portion that contacts the target drug solution is made of a fluorine-based resin. The resonant frequency of the quartz crystal oscillator changes according to the amount of impurities adsorbed on the adsorption layer. The detected change in the resonance frequency is used to manage the purity of the target medical liquid by comparing whether the change is within a preset allowable range of the change in the resonance frequency based on the purity of the target medical liquid.

16. The measuring device according to claim 15, wherein The measuring device further includes a display unit that displays the amount of change in the resonant frequency.

17. The measuring device according to claim 15 or 16, wherein The supply unit supplies the target chemical solution to the quartz crystal oscillator sensor by causing the target chemical solution to flow in one direction.

18. The measuring device according to claim 15 or 16, wherein The supply unit circulates the target chemical solution and supplies it to the quartz crystal oscillator sensor, and the circulation flow rate of the target chemical solution is 0.01 to 1000 ml / s.

19. The measuring device according to claim 15 or 16, wherein The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

20. The measuring device according to claim 15 or 16, wherein The quartz crystal oscillator sensor has a plurality of adsorption layers. The detection unit detects the amount of change in the resonant frequency for each of the plurality of adsorption layers.

21. The measuring device according to claim 20, wherein At least one of the plurality of adsorption layers is an Au layer.

22. The measuring device according to claim 15 or 16, wherein The measuring device further comprises: A sealing portion, configured on the quartz crystal oscillator sensor; a block body, which is arranged on the quartz crystal oscillator sensor via the sealing portion and is provided with a supply channel for supplying the target chemical solution to the quartz crystal oscillator sensor and a discharge channel for discharging the target chemical solution from the quartz crystal oscillator sensor; and The liquid delivery part is composed of a first hose connected to the supply channel and a second hose connected to the discharge channel. At least one of the liquid contact portion of the seal portion in contact with the target drug liquid, the liquid contact portion of the block in contact with the target drug liquid, and the liquid contact portion of the liquid feeding portion in contact with the target drug liquid is formed of a fluorine-based resin.

23. The measuring device according to claim 22, wherein The liquid contact portion of the block that contacts the target drug solution is made of a fluorine-based resin having a tensile strength of 20 to 60 MPa and a Shore D hardness of 60 to 80.

24. The measuring device according to claim 22, wherein The liquid contact portion of the block that contacts the target drug solution is formed of a fluorine-based resin selected from the group consisting of perfluoroalkoxyalkanes, ethylene tetrafluoroethylene copolymers, perfluoroethylene propylene copolymers, polytrifluorochloroethylene, and polyvinylidene fluoride.

25. The measuring device according to claim 22, wherein The liquid contact portion of the liquid delivery portion that contacts the target drug solution is formed of a fluorine-based resin having repeating units containing fluorine atoms, carbon atoms, and atoms other than fluorine atoms and carbon atoms.

26. The measuring device according to claim 22, wherein The liquid contact portion of the liquid delivery portion that contacts the target drug solution is formed of a fluorine-based resin selected from the group consisting of a ternary copolymer of tetrafluoroethylene, hexafluoropropylene, and vinylidene fluoride, polyvinylidene fluoride, an ethylene tetrafluoroethylene copolymer, and polychlorotrifluoroethylene.

27. The measuring device according to claim 22, wherein The liquid contact portion of the sealing portion that contacts the target drug solution is made of a fluorine-based resin having a tensile strength of 20 to 40 MPa, a Shore D hardness of 56 to 70, and a flexural modulus of elasticity of 0.5 to 3 GPa.

28. The assay device according to claim 22, wherein The liquid contact portion of the sealing portion that contacts the target drug solution is formed of a fluorine-based resin selected from the group consisting of perfluoroalkoxyalkanes, perfluoroethylene-propylene copolymers, ethylene-chlorotrifluoroethylene copolymers, ethylene-tetrafluoroethylene copolymers, polychlorotrifluoroethylene, and polyvinylidene fluoride.

29. A quartz crystal oscillator sensor used in the measuring device according to any one of claims 15 to 28, the quartz crystal oscillator sensor comprising a quartz crystal oscillator and an adsorption layer disposed on the quartz crystal oscillator. The adsorption layer is composed of at least one material selected from the group consisting of Si, Au, SiO2, SiOC, Cu, Co, W, Ti, TiN, Ta, TaN, and a photosensitive resin composition.

30. The quartz crystal oscillator sensor according to claim 29, wherein: At least two of the adsorption layers are arranged on the quartz crystal oscillator.

31. The quartz crystal oscillator sensor according to claim 30, wherein: At least one of the plurality of adsorption layers is an Au layer.

32. A kit comprising a medical solution and an information display unit for displaying or storing resonance frequency information of the medical solution, a method for determining a change in the resonant frequency of a quartz crystal oscillator caused by contacting the chemical liquid with a quartz crystal oscillator sensor including an adsorption layer that adsorbs impurities in the chemical liquid and a quartz crystal oscillator; comparing the obtained change in the resonant frequency with a change in the resonant frequency based on a predetermined purity of the chemical liquid; and providing an evaluation of the purity of the chemical liquid relative to the obtained change in the resonant frequency. Based on the evaluation, the obtained change in the resonant frequency and the purity of the chemical liquid are associated with each other and recorded as the resonant frequency information of the chemical liquid. The resonance frequency information of the liquid medicine is used to obtain information on the purity of the liquid medicine. The resonance frequency of the quartz crystal oscillator changes depending on the amount of impurities adsorbed on the adsorption layer.

33. The kit of claim 32, wherein: The kit includes a container for storing the medical solution, and the information display unit is provided in the container.

34. A kit according to claim 32 or 33, wherein The resonance frequency information of the medical solution is displayed on the information display unit using at least one of characters, symbols, and barcodes.

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