Automatic analysis device, automatic analysis method, and method for forming film of pressure sensor unit

Abstract

The invention provides an automatic analysis device and the like which do not remain air bubbles in the device. The automatic analysis device (1) is provided with a dispensing mechanism (100). This dispensing mechanism (100) is provided with: nozzles (sample dispensing nozzle (10), reagent dispensing nozzle (11), dispensing nozzle (102), dispensing nozzle (115)) that suck / discharge a liquid; a pressure generation mechanism (water supply pump (111)) that is connected to the nozzles and generates pressure for sucking / discharging the liquid; and a flow path (104) that measures the flow path including the nozzles and the pressure generation mechanism. A hydrophilic film (305) is formed on an inner surface (203a) of the pressure sensor unit (112), the hydrophilic film (305) containing a silicon compound and at least one of silica particles and alumina particles, and the hydrophilic film (305) is formed on the inner surface (203a) of the pressure sensor unit (112). The relationship between the arithmetic average roughness Ra0 of the base material (301) of the inner surface (203a) and the arithmetic average roughness Ra1 of the inner surface (203a) after the hydrophilic film (305) is formed is 0.8 * Ra0 < = Ra1.

Description

Technical Field

[0001] The present invention relates to an automatic analysis device, an automatic analysis method, and a film forming method for a pressure sensor unit. Background Art

[0002] Automated analyzers are used in hospitals and many medical research institutions. These automated analyzers analyze body components, such as blood, to detect abnormal values ​​of biological components or to analyze biological components to determine the presence or absence of disease.

[0003] The automatic analyzer is equipped with a dispensing mechanism for injecting a sample or reagent from a sample container containing a liquid sample or a reagent container containing a reagent into a reaction container for mixing the sample and reagent in an appropriate ratio by a suction / dispensing operation called dispensing.

[0004] Because the dispensing mechanism requires extremely high dispensing accuracy, the dispensing channel is typically filled with a liquid such as purified water (hereinafter referred to as system water) to accurately transmit the pressure generated by the pressure-generating mechanisms within the dispensing mechanism, such as the syringe and diaphragm. Furthermore, to ensure dispensing with high accuracy, the dispensing mechanism is equipped with a pressure sensor unit.

[0005] The pressure sensor unit consists of a sensor portion that measures pressure using a diaphragm, and a connection container that branches the system water from the pressure-receiving surface of the diaphragm toward the dispensing nozzle and syringe. Because the pressure sensor unit measures pressures in the range of approximately -100 to 100 kPa with high sensitivity, the diameter of the diaphragm attached to its tip needs to be large. Specifically, the diaphragm diameter is approximately 10 to 15 mm. Furthermore, the piping (flow path) connected to the pressure sensor unit's connection container is several millimeters in diameter, smaller than the diaphragm.

[0006] Therefore, if the diameter of the flow path in the pressure sensor unit's connection container is significantly increased from a few millimeters to 10-15 mm, the flow of system water in this area becomes turbulent and the flow rate decreases. This makes it easier for bubbles in the flow path to settle inside the connection container and the pressure sensor unit.

[0007] If the pressure applied to the pressure sensor unit increases during dispensing with attached bubbles, part of the pressure will shrink the bubbles, making it impossible to accurately measure the pressure. Consequently, it is impossible to dispense the correct amount of liquid.

[0008] Therefore, Patent Document 1 describes a method with the following structure: one of the two liquid inflow and outflow outlets in the connection container of the pressure sensor unit is set near the diaphragm, and when system water flows into the connection container, it moves in a manner that vortexes are rolled up near the diaphragm surface to remove bubbles.

[0009] By adopting this configuration, bubbles inside the pressure sensor unit are removed to a certain extent.

[0010] Prior art literature

[0011] Patent Literature

[0012] Patent Document 1: Japanese Patent Application Laid-Open No. 2005-274471 Summary of the Invention

[0013] Problems to be solved by the invention

[0014] However, even when the technology of Patent Document 1 is applied, bubbles remain inside the pressure sensor unit due to its structure, which sometimes reduces the pressure measurement accuracy. Therefore, there is a desire to improve the structure, but in many cases, structural changes are difficult while effectively utilizing general-purpose products.

[0015] The present invention has been made in view of the above-mentioned situation and has as its object to provide an automatic analysis device, an automatic analysis method, and a pressure sensor unit film forming method that do not leave bubbles inside.

[0016] Solutions to Problems

[0017] The inventors have conducted intensive research and development to solve the above problems and have found that the above problems can be solved by forming a hydrophilic film having a contact angle with water of 15° or less on the inner surface of the pressure sensor unit, thereby completing the present invention.

[0018] The automatic analysis device of the present invention that solves the above-mentioned problems has a dispensing mechanism, which has a nozzle for sucking / discharging liquid, a pressure generating mechanism connected to the nozzle and generating pressure for sucking / discharging liquid, and a pressure sensor unit for measuring the pressure in the flow path including the above-mentioned nozzle and the above-mentioned pressure generating mechanism. A hydrophilic film composed of at least one of silica particles and alumina particles and a silicon compound is formed on the inner surface of the above-mentioned pressure sensor unit, and the relationship between the arithmetic mean roughness Ra0 of the substrate of the above-mentioned inner surface and the arithmetic mean roughness Ra1 of the inner surface after the above-mentioned hydrophilic film is formed is 0.8×Ra0≤Ra1.

[0019] The effects of the invention are as follows.

[0020] According to the present invention, it is possible to provide an automatic analysis device, an automatic analysis method, and a method for forming a film of a pressure sensor unit in which no bubbles remain inside.

[0021] The following description of the embodiments will make other problems, structures, and effects clearer. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is an explanatory diagram showing an example of the overall configuration of an automatic analyzer according to one embodiment of the present invention.

[0023] Figure 2 This is an explanatory diagram showing another example of the overall configuration of the automatic analyzer according to one embodiment of the present invention.

[0024] Figure 3 This is a schematic diagram showing an example of a dispensing mechanism of an automatic analyzer according to one embodiment of the present invention.

[0025] Figure 4 This is a schematic diagram showing another example of the dispensing mechanism of the automatic analyzer according to one embodiment of the present invention.

[0026] Figure 5 This is a schematic cross-sectional view showing an example of a pressure sensor unit of an automatic analyzer according to an embodiment of the present invention.

[0027] Figure 6 This is a schematic cross-sectional view showing another example of the pressure sensor unit of the automatic analyzer according to one embodiment of the present invention.

[0028] Figure 7 This is a schematic cross-sectional view showing still another example of the pressure sensor unit of the automatic analyzer according to one embodiment of the present invention.

[0029] Figure 8 This is a cross-sectional view (SEM image) of a hydrophilic film composed of silica particles and a silica binder.

[0030] Figure 9 It is a graph showing the relationship between the film thickness (nm) of the hydrophilic film and the contact angle (°) with water.

[0031] Figure 10 It is a graph showing the relationship between the ratio (mass %) of silica particles in the hydrophilic film and the contact angle (°) with water.

[0032] Figure 11 Graph showing the relationship between the ratio (mass %) of SiO 2 particles in a hydrophilic film and the contact angle (°) with water.

[0033] Figure 12A This is a schematic diagram of a cross section of a roughened surface on which a hydrophilic film is formed.

[0034] Figure 12B This is a schematic diagram of a cross section of a roughened surface on which a hydrophilic film is formed.

[0035] Figure 12C This is a schematic diagram of a cross section of a roughened surface on which a hydrophilic film is formed.

[0036] Figure 13A It is an explanatory diagram for explaining the step of forming a hydrophilic film on the inner surface of the connection container.

[0037] Figure 13B It is an explanatory diagram for explaining the step of forming a hydrophilic film on the inner surface of the connection container.

[0038] Figure 13C It is an explanatory diagram for explaining the step of forming a hydrophilic film on the inner surface of the connection container.

[0039] Figure 14 This is an explanatory diagram showing a cut portion when measuring the surface roughness of the inner surface of a connection container. DETAILED DESCRIPTION

[0040] Hereinafter, an automatic analysis device, an automatic analysis method, and a pressure sensor cell film forming method according to an embodiment of the present invention will be described in detail with reference to the drawings as appropriate.

[0041] (1) Automatic analysis device

[0042] Figure 1 This is an explanatory diagram showing an example of the overall configuration of an automatic analyzer according to one embodiment of the present invention. Figure 2 This is an explanatory diagram showing another example of the overall configuration of the automatic analyzer according to one embodiment of the present invention.

[0043] like Figure 1 As shown, an automatic analyzer 1 reacts a sample of a test object with a reagent to analyze specific components in the sample. The automatic analyzer 1 is generally configured to include a reagent container loading unit 3 for loading reagent containers 2 filled with reagents, a reagent cooling box 4 containing the reagent container loading unit 3, and a rack transport line 7 serving as a transport line on which racks 6 are mounted, each of which holds a sample container 5.

[0044] In addition, the automatic analysis device 1 is provided with a disc-shaped culture plate 9 that can accommodate a large number of reaction containers 8, a sample dispensing nozzle 10 as a nozzle for dispensing samples, a reagent dispensing nozzle 11 as a nozzle for dispensing reagents, and a reaction container transport mechanism 12 as a mechanism for transporting the reaction containers 8.

[0045] As described above, a plurality of reaction containers 8 can be placed on the culture tray 9. The culture tray 9 is mounted so as to be able to move the reaction containers 8 placed in the circumferential direction to predetermined positions by rotation.

[0046] In the automatic analyzer 1 , as described above, the sample container 5 holding the sample is mounted on the rack 6 , and the sample container 5 is moved to the sample dispensing position 13 near the sample dispensing nozzle 10 by the rack transport line 7 .

[0047] A sample dispensing head / reaction vessel transport mechanism 14 is provided near the culture plate 9, capable of movement in three directions: the X-axis, the Y-axis, and the Z-axis. The sample dispensing head / reaction vessel transport mechanism 14 is mounted so as to be movable within a range encompassing a sample dispensing head / reaction vessel holding member 15, a reaction vessel stirring mechanism 16, a sample dispensing head / reaction vessel disposal port 17, a sample dispensing head mounting position 18, and a predetermined portion of the culture plate 9. This mechanism transports the sample dispensing head and reaction vessel 8.

[0048] The sample dispensing head / reaction vessel holding member 15 is equipped with a plurality of unused reaction vessels 8 and a plurality of sample dispensing heads. Therefore, the sample dispensing head / reaction vessel transport mechanism 14 moves above the sample dispensing head / reaction vessel holding member 15, descends, and then ascends while grasping an unused reaction vessel 8. Subsequently, the sample dispensing head / reaction vessel transport mechanism 14 moves above a predetermined position on the culture tray 9, descends, and mounts the unused reaction vessel 8 on the culture tray 9.

[0049] The sample dispensing head / reaction vessel transport mechanism 14 then moves above the sample dispensing head / reaction vessel holding member 15, then descends and rises to pick up an unused sample dispensing head. Furthermore, the sample dispensing head / reaction vessel transport mechanism 14 moves above the sample dispensing head mounting position 18, where it descends and sets the sample dispensing head in the sample dispensing head mounting position 18.

[0050] The sample dispensing nozzle 10 is capable of rotating and moving vertically. After rotating to a position above the sample dispensing head mounting position 18, the sample dispensing nozzle 10 descends and the sample dispensing head is mounted on the tip of the sample dispensing nozzle 10. The sample dispensing nozzle 10, with the sample dispensing head mounted, then moves to a position above the sample container 5 held by the stage 6. It then descends and aspirates a predetermined amount of sample held in the sample container 5.

[0051] Next, the sample dispensing nozzle 10 having sucked the sample moves to above the culture disk 9 and then descends to discharge the sample into an unused reaction vessel 8 held on the culture disk 9. Upon completion of sample discharge, the sample dispensing nozzle 10 is discarded from the sample dispensing head / reaction vessel discard port 17.

[0052] A plurality of reagent containers 2 are loaded into the reagent container loading section 3 disposed inside the reagent cooling box 4. Furthermore, a lid 19 of the reagent cooling box 4 is provided on top of the reagent container loading section 3, so that the reagent cooling box 4 can keep the interior thereof at a predetermined temperature.

[0053] The cover 19 does not cover a part of the cold storage box, but there is a loader ( Figure 1(not shown in the figure).

[0054] A reagent suction hole 20, serving as a through-hole for reagent suction, is provided in a portion of the lid 19. Furthermore, the reagent dispensing nozzle 11 is capable of rotating and moving up and down. After rotating and moving to a position above the reagent suction hole 20 provided in the lid 19 of the reagent cooler 4, it descends and passes through the reagent suction hole 20. After passing through the reagent suction hole 20, the reagent dispensing nozzle 11 places its tip into the reagent in the designated reagent container 2, sucking a predetermined amount of reagent. The reagent dispensing nozzle 11 then ascends and rotates to a position above a predetermined position on the culture tray 9, dispensing the reagent into the reaction container 8 provided on the culture tray 9.

[0055] After the sample and reagents have been dispensed, the reaction vessel 8 is moved to a predetermined position by the rotation of the culture plate 9 and then transported to the reaction vessel stirring mechanism 16 by the sample dispensing head / reaction vessel transport mechanism 14. The reaction vessel stirring mechanism 16 imparts rotational motion to the reaction vessel 8, thereby stirring and mixing the sample and reagents within the reaction vessel 8. After stirring, the reaction vessel 8 is returned to the predetermined position on the culture plate 9 by the sample dispensing head / reaction vessel transport mechanism 14.

[0056] The reaction vessel transport mechanism 12 is capable of rotation and vertical movement. After the sample and reagent are dispensed and stirred and a predetermined reaction time has elapsed in the culture plate 9, it moves to the top of the reaction vessel 8 and then descends to hold the reaction vessel 8. The reaction vessel 8 is then transported to the detection unit 21 by the rotation of the reaction vessel transport mechanism 12, where the analysis results of specific components in the sample are determined.

[0057] In addition, by Figure 1 The control unit 103 (see FIG. 1 ) of the computer or the like of the automatic analysis device 1 not shown in FIG. Figure 3 、 Figure 4 ) controls the drive and drive timing of the above various components.

[0058] Figure 2 Most of the automatic analysis device 22 shown is also similar to Figure 1 The automatic analyzer 1 shown is universal, and therefore different parts are described.

[0059] First, the automatic analyzer 22 is a type that does not have a tip at the tip of the sample dispensing nozzle 23 or the reagent dispensing nozzle 24. After the sample and reagent are aspirated and discharged from these nozzles, the tip of the automatic analyzer 22 is not replaced, but the tip is placed in the nozzle cleaning mechanism 25 for cleaning.

[0060] In the automatic analyzer 22 , the measurement unit 26 quantifies the color intensity, turbidity, and the like of the reagent / sample mixture in the reaction container 8 .

[0061] (2) Injection mechanism

[0062] Figure 3 This is a schematic diagram showing an example of a dispensing mechanism of an automatic analyzer according to one embodiment of the present invention. Figure 4 This is a schematic diagram showing another example of the dispensing mechanism of the automatic analyzer according to one embodiment of the present invention.

[0063] like Figure 3 As shown, in the dispensing mechanism 100, a dispensing nozzle 102 (equivalent to the sample dispensing nozzle 10 and the reagent dispensing nozzle 11) for dispensing samples and reagents is equipped with a detachable suction head 101 (equivalent to the sample dispensing head and suction head) and the like. Figure 1 This is controlled by the control unit 103.

[0064] The dispensing nozzle 102 is connected to the syringe 105 via a flow path 104, and the interior of the syringe 105 is filled with system water 106. The syringe 105 has a cylinder 107 and a plunger 108. The plunger 108 is driven by a control unit 103. The control unit 103 drives the plunger 108 in the up and down directions relative to the syringe 105, thereby sucking and ejecting the liquid sample and liquid reagent at the suction head 101 assembled on the dispensing nozzle 102. The syringe 105 has a flow path 118 that communicates with the water supply tank 109. The flow path 118 is provided with an electromagnetic valve 110 and a water supply pump 111 as a pressure generating mechanism. System water 106 is stored in the water supply tank 109, and the system water 106 is ejected from the dispensing nozzle 102 by driving the water supply pump 111, thereby cleaning the interior of the dispensing nozzle 102. This cleaning is performed before dispensing the sample or reagent, thereby minimizing the mixing of contaminants of the dispensing nozzle 102 into the sample or reagent during dispensing.

[0065] The pressure sensor unit 112 is located in the flow path 104 between the dispensing nozzle 102 and the syringe 105. The pressure sensor unit 112 uses the pressure sensor 113 to measure the pressure within the flow path 104, including the nozzle (dispensing nozzle 102) and the pressure generating mechanism (water supply pump 111), and transmits the result to the control unit 103.

[0066] Figure 4 Most of the dispensing mechanism 114 shown is also similar to Figure 3 The dispensing mechanism 100 shown is common, so different parts are described.

[0067] First, the dispensing mechanism 114 is a type that does not have a tip attached to the tip of the dispensing nozzle 115. After the dispensing nozzle 115 has completed aspiration and dispensing of the sample and reagent, the tip is not replaced. Instead, the tip of the nozzle is placed in a nozzle cleaning mechanism 117 filled with cleaning water 116 for cleaning.

[0068] (3) Pressure sensor unit

[0069] The above-mentioned pressure sensor unit 112 will be described in detail.

[0070] Figure 5 This is a schematic cross-sectional view showing an example of a pressure sensor unit of an automatic analyzer according to an embodiment of the present invention. Figure 6 This is a schematic cross-sectional view showing another example of the pressure sensor unit of the automatic analyzer according to one embodiment of the present invention. Figure 7 This is a schematic cross-sectional view showing still another example of the pressure sensor unit of the automatic analyzer according to one embodiment of the present invention.

[0071] As reference Figure 3 、 Figure 4 Explain that, Figure 5 The pressure sensor unit 112 shown is located in the flow path 104 between the dispensing nozzle 102 (dispensing nozzle 115) and the syringe 105. The pressure sensor unit 112 comprises a pressure sensor 202 with a diaphragm 201 for measuring pressure, and a connection container 203, which serves as the housing for the pressure sensor unit 112. Furthermore, an O-ring 204 is installed between the pressure sensor 202 and the connection container 203 to prevent leakage of the system water 106. This structure, in which the O-ring 204 is inserted into the connection container 203, further improves pressure resistance.

[0072] In this embodiment, a hydrophilic film 305 containing or consisting of silica particles or alumina particles and a silicon compound is formed on the inner surface 203a of the pressure sensor unit 112 (specifically, the connection container 203) (see Figure 8 12). In this way, by making the inner surface 203a of the pressure sensor unit 112 hydrophilic with the hydrophilic film 305, the inner surface 203a becomes hydrophilic and becomes an air-repellent surface that repels air. Therefore, bubbles are prevented from adhering, achieving a bubble-free state.

[0073] Furthermore, in this embodiment, the base material 301 (see Figure 8 、 Figures 12A to 12CThe relationship between the arithmetic average roughness Ra0 of the inner surface 203a after the hydrophilic film 305 is formed and the arithmetic average roughness Ra1 of the inner surface 203a is 0.8×Ra0≤Ra1. By roughening the inner surface 203a in this manner, the hydrophilicity is further improved, and the bubble-free state is further achieved. To further achieve this effect, in this embodiment, the arithmetic average roughness is preferably 0.85×Ra0≤Ra1, more preferably 0.9×Ra0≤Ra1, even more preferably 0.95×Ra0≤Ra1, and most preferably 0.97×Ra0≤Ra1.

[0074] Furthermore, when the O-ring 204 is configured to extend into the interior of the connection container 203, that is, when there is a point where the O-ring 204 contacts the system water 106, bubbles generated in the system water 106, the flow path 104, etc., also come into contact with the O-ring 204. Consequently, there is a risk that bubbles may remain on the surface of the O-ring 204, affecting pressure sensing. Therefore, in this case, a hydrophilic film 305 is also formed on the O-ring 204, further eliminating bubbles within the connection container 203.

[0075] The connection points 205 and 206 between each flow path 104 from the dispensing nozzle 102 (dispensing nozzle 115) and the syringe 105 and the pressure sensor unit 112 have inflow and outflow ports 205a and 206a for the system water 106 to flow into or out of the pressure sensor unit 112. The openings of the inflow and outflow ports 205a and 206a are connected to the opening of the flow path 104. Figure 5 The connection portions 205 and 206 shown are connected to the flow path 104 by screwing, but any connection method having pressure resistance may be used, and the connection to the flow path 104 may be made by press-fitting or the like.

[0076] In this embodiment, when the cross-sectional area of ​​each of the liquid inflow and outflow ports 205a and 206a of the pressure sensor unit 112, i.e., the area of ​​the flow path opening at the connection portions 205 and 206, is denoted as α, and the area of ​​the pressure-receiving surface (diaphragm 201) of the pressure sensor unit 112 is denoted as β, it is preferable that α < β. This improves the sensitivity of pressure sensing.

[0077] Figure 5 In the embodiment, the inner surface of the pressure sensor unit 112 (the inner surface of the connection container 203) is conical and is arranged so that the apex of the cone is vertically upward. A liquid inflow outlet 205a (connected to the nozzle (dispensing nozzle 102)) is provided at the apex of the cone. Figure 5 The bottom surface of the cone is provided with a liquid inlet and outlet 206a (connected to a pressure generating mechanism (water supply pump 111)) in the tangential direction of the cone bottom surface. Figure 5Furthermore, the pressure-receiving surface (diaphragm 201) of the pressure sensor unit 112 is arranged on the bottom surface of the cone.

[0078] System water 106 flowing into connection container 203 from inflow outlet 206a, provided tangentially to the bottom circumference, generates a swirling flow along the circumferential surface of connection container 203 as it flows toward inflow outlet 205a at the apex, and then flows out from inflow outlet 205a at the apex. Pressure sensor unit 112 utilizes this swirling flow to remove bubbles from connection container 203.

[0079] For pressure resistance, connecting container 203 is preferably made of a resin such as acrylic or polycarbonate. When manufacturing connecting container 203, the resin block can be formed by mechanical processing. However, to prevent deformation due to heat generation, it is best to submerge the block in water or spray water on the block surface to cool it while processing. The arithmetic average roughness (Ra) of the inner surface of connecting container 203 used in this embodiment was measured, and while varying depending on the batch, it ranged from 100 to 300 nm.

[0080] In this embodiment, a hydrophilic film 305 is formed on the conical inner surface 203a of the connection container 203 to remove bubbles in the connection container 203, thereby reducing the retention of bubbles inside the connection container 203 and further improving the pressure measurement accuracy at the diaphragm 201.

[0081] In addition, the shape of the pressure sensor unit 112 (the shape of the connection container 203) is not limited to Figure 5 Conical shape shown.

[0082] For example, Figure 6 As shown, the pressure sensor unit 112 can be configured by connecting the interior of the container 203 with a cone and a cylinder. In this case, the inflow / outflow port 206a is preferably formed in the cylindrical portion rather than the conical portion. The cylindrical portion has the advantage of being easier to process than the conical portion.

[0083] And, for example Figure 7 As shown, the pressure sensor unit 112 can be configured to have a cylindrical interior connected to the container 203 and to have rounded corners on the top. This rounded structure can also suppress the accumulation of bubbles at the top corners.

[0084] Figures 5 to 7In the example, if the cross section of the gap in the connection container 203 gradually increases from the inflow outlet 205a at the top of the pressure sensor unit 112 to the diaphragm 201 as the pressure receiving part of the pressure sensor 202, it is difficult to generate turbulent flow of the system water 106 in the connection container 203. From this point of view, it can be said that the pressure sensor unit 112 Figure 5 The conical configuration shown is most suitable.

[0085] (4) Hydrophilic membrane

[0086] a) Overview of the composition and formation method of the hydrophilic film coating liquid

[0087] The hydrophilic film 305 in this embodiment is produced by applying a hydrophilic film coating liquid to the interior of the connection container 203 and then curing the liquid. Specifically, the hydrophilic film coating liquid comprises at least one of hydrophilic silicon dioxide (silica) particles (silicon dioxide particles) and aluminum oxide (alumina) particles (alumina particles), a binder for retaining the particles, and an organic solvent for dispersing or dissolving the materials. The binder is preferably an alkoxysilane compound whose main component becomes silicon dioxide when heated.

[0088] In this embodiment, by specifying the size of the silica and alumina particles, the hydrophilicity of the hydrophilic film 305 is further increased, further contributing to the elimination of bubbles. Furthermore, by specifying the addition rate of the silica and alumina particles, the hydrophilicity of the hydrophilic film 305 is further increased, further contributing to the elimination of bubbles.

[0089] Figure 8 This is a cross-sectional view (scanning electron microscope image (SEM image)) of a hydrophilic film containing silica particles and a silica binder. Figure 8 The hydrophilic film 305 shown uses silicon dioxide particles 302 as a hydrophilic material.

[0090] like Figure 8 As shown, a hydrophilic film 305 is formed on a substrate 301. The hydrophilic film 305 comprises silica particles 302, a silica binder 304 (see Figures 12A to 12C), and the gaps 303 therebetween. A silica binder 304 is thinly attached between the multiple silica particles 302 and to the substrate 301, maintaining the film structure. The contact angle of silica itself with water is approximately 30°, but the fine irregularities created by the silica particles 302 on the surface of the hydrophilic film 305 and the gaps 303 on the surface reduce the contact angle with water. Furthermore, capillary action allows condensed water to penetrate the gaps between the silica particles 302 and the gaps 303, further reducing the contact angle between the surface of the hydrophilic film 305 and water. This allows the formation of a hydrophilic film 305 with a contact angle with water of 15° or less.

[0091] Furthermore, even when alumina particles are used instead of the silica particles 302 , the same film structure is achieved and the same effects are obtained.

[0092] b) Hydrophilic film coating liquid for forming a hydrophilic film and its composition

[0093] The hydrophilic film coating liquid is prepared by dispersing and dissolving at least one of silica particles and alumina particles and a precursor of a silica binder in an organic solvent. The organic solvent is an alcohol-based solvent. The three materials mentioned above are described below.

[0094] b-1) Hydrophilic materials

[0095] In this embodiment, at least one of silica particles and alumina particles is used as the hydrophilic material. The average particle size of the particles is preferably 10 to 50 nm, more preferably 10 to 20 nm. The reasons for this are described below.

[0096] The average particle size of the particles can be measured using a particle size analyzer LA-950V2 manufactured by Horiba, Ltd.

[0097] Hydrophilicity:

[0098] The hydrophilicity of silica and alumina particles is exerted by their surface. For example, in silica particles, the bonds between silicon and oxygen partially break, exposing hydroxyl groups, which is believed to contribute to hydrophilicity. Similarly, in alumina particles, the bonds between aluminum and oxygen partially break, exposing hydroxyl groups, which is believed to contribute to hydrophilicity. Therefore, the larger the surface area per unit mass of a particle, the greater the number of hydroxyl groups exposed per unit mass, thereby enhancing hydrophilicity. The smaller the particle size, the greater the surface area per unit mass, thus exerting a stronger hydrophilicity.

[0099] On the other hand, if the particle diameter increases, the gaps between the particles after film formation become larger, and the number of gaps between the particles decreases. Therefore, compared with the case of using particles with smaller particle diameters, capillary action is less likely to occur. Therefore, if the particle diameter increases, it is difficult to improve the hydrophilicity.

[0100] Dispersion stability in hydrophilic membrane coating liquid:

[0101] Regarding the density of the above particles, the silica particles are 2.5 to 2.6 g / cm 3 , alumina particles are 3.9~4.1g / cm 3 , with the following solvents 0.8 ~ 1.0g / cm 3 The particles are considerably larger than the hydrophilic film coating liquid. Therefore, if the particle diameter of the particles is large, they will settle in the hydrophilic film coating liquid. If the particle size is 70 nm or larger for silica particles and 50 nm or larger for alumina particles, significant settling will occur. Therefore, if the particle diameter is large, it is necessary to stir the particles before use to disperse them throughout the hydrophilic film coating liquid. Therefore, for the reasons mentioned above, the preferred average particle size of the particles is 50 nm or smaller.

[0102] While the above description assumes spherical particles, some particles may have a spherical shape consisting of several to dozens of connected particles. In such cases, sufficient dispersibility is preferred if the size of a single spherical particle is 50 nm or less. From this perspective, and for the reasons mentioned above, the preferred average particle size is also 50 nm or less.

[0103] Leveling relative to the substrate:

[0104] When coating a substrate 301 having an uneven surface, the surface unevenness becomes smaller because the particles fill the valley to a certain extent. This can be confirmed by the reduction of the arithmetic surface roughness (Ra). If Ra becomes smaller, the actual surface area becomes smaller, so the number of hydroxyl groups of the silica particles and alumina particles per unit area of ​​the projected area decreases, and the desired hydrophilicity may not be obtained. The larger the particles, specifically when using particles with an average particle size of 30nm or more, the stronger the tendency to fill the valley. In the case of an average particle size of 10 to 20nm, the effect of filling the valley is small, and the coating is applied without filling the valley along the uneven shape, so Ra basically does not change, and a higher hydrophilicity can be imparted. From this point of view, based on the above reasons, the more preferred average particle size is 10 to 20nm.

[0105] ·deal with:

[0106] If the particles are too small, specifically if the average particle size is less than 10 nm, there is a concern that they may become airborne dust during weighing or mixing. Inhalation of these airborne particles may cause respiratory distress. Therefore, the average particle size of the silica and alumina particles used is preferably 10 nm or larger. From this perspective, and for the reasons stated above, an average particle size of 10 nm or larger is preferred.

[0107] b-2) Adhesive

[0108] The hydrophilic film 305 of one embodiment is a binder whose main component after film formation is silicon dioxide. Silica is insoluble in organic solvents, but some of its precursors are soluble in organic solvents. In this embodiment, a silica precursor soluble in organic solvents is used.

[0109] Specific examples of such silica precursors include hydrolyzable silicon compounds that transform into silica through hydrolysis. The most common hydrolyzable silicon compound is generally called silica sol. This is a polymer with an average molecular weight of several thousand to tens of thousands, formed by partial hydrolysis of multiple tetraalkoxysilanes, which release alkoxy groups and form silicon-oxygen-silicon bonds among the molecules.

[0110] Silica sol is soluble in alcoholic solvents such as methanol and ethanol. Tetraethoxysilane is the most readily used tetraalkoxysilane. Because tetramethoxysilane, which has a shorter alkyl chain, is highly reactive with water, the hydrophilic film coating liquid forming the hydrophilic film 305 may solidify if stored in a high-humidity environment for a long time. Furthermore, since tetrapropoxysilane and tetrabutoxysilane, which have longer alkyl chains than tetraethoxysilane, are less susceptible to hydrolysis, the post-coating heat curing time tends to be prolonged, or the heat curing reaction tends to be slowed down if the heating temperature is not increased. Therefore, tetraethoxysilane is preferred as the tetraalkoxysilane used to form silica sol.

[0111] In addition to silica sol, which is a polymer of alkoxysilane, compounds having three alkoxy groups on a silicon atom having four bond groups in the molecule and other bond groups other than alkoxy groups, such as a benzene ring or an alkyl chain, can also be used as a precursor of the silica binder 304. When such materials are used, the main component of the hydrophilic film 305 is silica, but in addition, the film also contains atoms such as carbon, nitrogen, and sulfur.

[0112] Specific examples of such compounds include methyltrimethoxysilane, dimethyldimethoxysilane, phenyltrimethoxysilane, phenyltriethoxysilane, methyltriethoxysilane, n-propyltrimethoxysilane, n-propyltriethoxysilane, vinyltrimethoxysilane, vinyltriethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, N-2-(aminoethyl)-3-aminopropyltrimethoxysilane, N-2-(aminoethyl)-3-aminopropyltriethoxysilane, 3-isocyanatepropyltrimethoxysilane, 3-isocyanatepropyltriethoxysilane, 3-mercaptopropyltrimethoxysilane, and 3-mercaptopropyltriethoxysilane.

[0113] b-3) Solvent

[0114] Conventional organic solvents are used as solvents for the hydrophilic membrane coating liquid. For ease of machining, the connecting container 203, which serves as the housing of the pressure sensor unit 112, is often made of resins such as acrylic acid and polycarbonate. However, depending on the type of solvent, there is a concern that these resins may dissolve or swell. Therefore, alcoholic solvents are preferred to prevent, or substantially prevent, dissolution or swelling of the resins. Specifically, preferred solvents include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, and tert-butanol, which have carbon atoms of 1 to 4. Since these solvents have a boiling point of approximately 60 to 120°C, they evaporate quickly after coating, which has the advantage of shortening the time required for film formation. Alcohols with a carbon number greater than that of butanol have difficulty dissolving hydrolyzable silicon compounds, and drying after coating takes time. Therefore, alcohols with carbon atoms of 5 or more are not recommended.

[0115] In addition to the above-mentioned alcohols, cellosolve-based solvents in which one of the hydroxyl groups of ethylene glycol is converted into a monoalkoxy group are also preferred for their ability to dissolve hydrolyzable silicon compounds. However, since most of these alcohols have high boiling points and are difficult to volatilize, it is desirable to expedite their volatilization by heating or reducing pressure after coating.

[0116] c) Film thickness (average film thickness)

[0117] Figure 9 Graph showing the relationship between the thickness (nm) of the hydrophilic film and the contact angle (°) with water.

[0118] Figure 9 The graph shows the result of forming a hydrophilic film 305 using a hydrophilic film coating liquid having a mass ratio of silicon dioxide particles 302 to a silica precursor of 1:1. The substrate 301 is an acrylic plate having an arithmetic surface roughness (Ra) of 10 nm and being visually flat. Figure 9 As shown, when the thickness of the hydrophilic film 305 is 40 nm or greater, the contact angle with water is reduced to below 15°, demonstrating sufficient hydrophilicity. Furthermore, when the thickness of the hydrophilic film 305 is 50 nm or greater, the contact angle with water is reduced to 10°, demonstrating even higher hydrophilicity. Even when aluminum oxide particles are used instead of the silica particles 302, the results are roughly the same as when the silica particles 302 are used. Therefore, the thickness of the hydrophilic film 305 in this embodiment is preferably 50 nm or greater. Furthermore, the film thickness of multiple arbitrary locations can be measured, and the average value (average film thickness) can be used to manage the film thickness.

[0119] d) Mixing ratio

[0120] The solid components in the hydrophilic film coating liquid forming the hydrophilic film 305 are at least one of the hydrophilic materials, silica particles 302 and alumina particles, and a silica precursor, which serves as a binder. Varying the ratio of these two components changes the performance of the hydrophilic film 305, specifically its contact angle with water. The contact angle of the hydrophilic film 305 formed by varying the ratio of silica particles 302 to the silica precursor to achieve a film thickness of approximately 100 nm was investigated. Figure 10 The results are shown.

[0121] Figure 10 It is a graph showing the relationship between the ratio (mass %) of silica particles in the hydrophilic film and the contact angle (°) with water.

[0122] Figure 10 The horizontal axis shows the proportion of silica particles 302. The proportion of the precursor of the silica binder 304 is the value obtained by subtracting the proportion of silica particles 302 from 100%. The average particle size of the silica particles 302 used here is 20 nm. The average particle size of the silica particles 302 was measured using a particle size analyzer LA-950V2 manufactured by Horiba Ltd. The contact angle was measured using a contact angle meter (model: CA-d) manufactured by Kyowa Interface Science Co., Ltd.

[0123] As the content of hydrophilic silica particles 302 increases, the contact angle with water decreases. In the case (a) where the hydrophilic film 305 is formed on a substantially flat acrylic plate with an Ra of 5 nm, the contact angle decreases to 10° when the content of silica particles 302 is 30% by mass or greater. However, when the content of silica particles 302 is 30% to 90% by mass, the contact angle remains constant and does not decrease further.

[0124] On the other hand, in the case (b) where the hydrophilic film 305 is deposited on an acrylic plate with an Ra of 100 nm, the contact angle decreases further compared to the case with an Ra of 5 nm. When the silica particles 302 content is 30-60% by mass, the contact angle decreases to 4-5°. In other words, depositing the film on a substrate with a higher Ra improves hydrophilicity.

[0125] It is known that if the actual surface area is larger than the projected surface area, a hydrophobic surface becomes more hydrophobic, and a hydrophilic surface becomes more hydrophilic. Therefore, it is believed that increasing Ra, that is, increasing the actual surface area relative to the projected surface area, increases hydrophilicity and reduces the contact angle.

[0126] Furthermore, in case (b), when the hydrophilic silica particles 302 were increased to 70% by mass or greater, the contact angle increased. In other words, a trend toward decreasing hydrophilicity was observed. This is believed to be because increasing the proportion of silica particles 302 allowed the silica particles 302 to enter the valleys of the roughened surface, lowering Ra and thus slightly increasing the contact angle.

[0127] When the Ra of the hydrophilic film 305 after formation was measured, the Ra of the hydrophilic film 305 containing 30% by mass of silica particles 302 with an average particle size of 20 nm was 92 nm. The Ra of the hydrophilic film 305 containing 60% by mass of the silica particles 302 was 82 nm. Furthermore, the Ra of the hydrophilic film 305 containing 65% by mass of the silica particles 302 was 61 nm. This demonstrates that the main reason for the increase in contact angle is that the increase in the proportion of silica particles 302 leads to a decrease in Ra. From the perspective of achieving sufficient hydrophilicity, the Ra of the hydrophilic film 305 is preferably 80 nm or greater (0.08 μm or greater).

[0128] It was found that even when using acrylic plates with Ra of 300 nm and 500 nm, as described above, when the content of silica particles 302 was 30 to 60 mass%, the contact angle decreased to 4 to 5°, which was approximately 3° lower than when the content of silica particles 302 was 20 mass% and 70 mass%.

[0129] From the above results, it was found that the content of the silica particles 302 , which is a hydrophilic material, in the solid content of the hydrophilic film coating liquid is preferably 30 to 60% by mass.

[0130] The same experiment conducted on alumina particles (average particle size 20 nm) revealed that the particle content is preferably 30-60% by mass, similar to the silica particles 302. The average particle size of the alumina particles was also measured using a particle size analyzer LA-950V2 manufactured by Horiba, Ltd.

[0131] Furthermore, the same experiment as above was conducted using two types of silica particles 302 with average particle diameters of 20 nm and 50 nm to form a hydrophilic film 305 on an acrylic plate with Ra of 100 nm. Figure 11 The results are shown.

[0132] Figure 11 Graph showing the relationship between the ratio (mass %) of SiO 2 particles in a hydrophilic film and the contact angle (°) with water.

[0133] like Figure 11As shown in Figure 2, in the case (b) of using silica particles 302 with an average particle size of 50 nm, the contact angle does not decrease from 12° when the content is 15% by mass or more. On the other hand, in the case (a) of using silica particles 302 with an average particle size of 20 nm, the contact angle decreases to 4-5° when the content is 30-60% by mass.

[0134] The Ra of the hydrophilic film 305 after formation was measured. The Ra of the hydrophilic film 305 containing 30% by mass of silica particles 302 with an average particle size of 20 nm was 92 nm. The Ra of the hydrophilic film 305 containing 60% by mass of silica particles 302 with an average particle size of 20 nm was 82 nm.

[0135] On the other hand, the Ra of the hydrophilic film 305 containing 30% by mass of silica particles 302 with an average particle size of 50 nm was 55 nm. The Ra of the hydrophilic film 305 containing 60% by mass of silica particles 302 with an average particle size of 50 nm was 30 nm.

[0136] and Figure 10 The results are the same, which shows that the decrease of Ra is the main reason for the increase of contact angle.

[0137] Based on the above results, it is believed that the contact angle can be reduced to 4-5° if the Ra of the hydrophilic film 305 after film formation is approximately 80% of the Ra of the substrate 301. It was found that if the Ra is further reduced, the contact angle will not be reduced that much.

[0138] Figures 12A to 12C The above results and reasons are schematically shown in FIG.

[0139] Figures 12A to 12C This is a schematic diagram of a cross section of a roughened surface on which a hydrophilic film is formed.

[0140] Figure 12A When the average particle size is 10 to 20 nm and the particle addition is 30 to 60 mass %, a hydrophilic film 305 composed of silica particles 302 or alumina particles and a silica binder 304 is formed along the concavo-convex surface of the substrate 301 .

[0141] on the other hand, Figure 12B When the average particle size is 40 nm or greater and the particle addition rate is 30 to 60% by mass, a hydrophilic film 305 comprising silica particles 302 or alumina particles and a silica binder 304 is formed along the concavo-convex surface of the substrate 301 .

[0142] Figure 12C When the average particle size is 10 to 20 nm and the particle addition rate exceeds 60 mass %, a hydrophilic film 305 composed of silica particles 302 or alumina particles and a silica binder 304 is formed along the concavo-convex surface of the substrate 301 .

[0143] like Figure 12B and Figure 12C As shown, the hydrophilic film 305 is formed so as to fill the valleys of the unevenness of the substrate 301. Therefore, it is considered that Ra decreases, the actual surface area decreases, and the hydrophilicity decreases.

[0144] The reason why the valleys are filled when the silica particles 302 and the alumina particles are large is considered to be as follows.

[0145] When the particle diameter is small, the surface area of ​​the particles per unit mass is large, so the interaction between the particle surface and the surface of the substrate 301 is large, and the particles are formed into a film in a manner arranged along the surface of the substrate 301 .

[0146] On the other hand, if the particle becomes larger, the surface area of ​​the particle per unit mass becomes smaller, and thus the interaction with the surface of the substrate 301 becomes smaller. Therefore, the gravity of the particle becomes dominant, and the particle settles to the valley portion of the substrate 301. As a result, it is believed that Figure 12B The membrane structure shown.

[0147] The reason why the valleys are filled when the particle ratio increases is that the thixotropy of the coating liquid increases when the particle amount increases, and it is estimated that the coating liquid is more likely to accumulate in the valleys of the substrate 301 .

[0148] e) Film Formation Method for Pressure Sensor Unit

[0149] The pressure sensor unit 112 is formed by applying a hydrophilic film coating liquid and thermally curing it.

[0150] (i) Coating (screwing process, coating process)

[0151] Use a dropper or the like to apply the hydrophilic film coating liquid to the connected container 203. Figures 5 to 7 As shown, the connection points 205 and 206 connecting the connection container 203 to the piping (flow path 104) are screw-in connections. However, if a hydrophilic film coating liquid is deposited on these screw-in portions to form a hydrophilic film 305, there is a risk that system water 106 may leak from the connection points 205 and 206 when high pressure is applied to the pressure sensor unit 112 after film formation. This is believed to occur when the system water 106 migrates through the gaps 303 formed in the hydrophilic film 305 due to capillary action.

[0152] When applying the hydrophilic film coating liquid, a pipe or resin screw 207 is screwed into the connection parts 205 and 206 in advance (see Figure 13A) etc., so that the hydrophilic film coating liquid does not adhere to the screwed-in portion during application, thereby eliminating this concern. Specifically, this concern can be eliminated by not forming the hydrophilic film 305 on the surfaces of the inflow outlets 205a and 206a that contact the flow path 104 (more specifically, the surfaces of the connection portions 205 and 206 that contact the flow path 104). Furthermore, after application of the hydrophilic film coating liquid, if the solvent evaporates, there is no concern that the hydrophilic film coating liquid will adhere to the screwed-in portion. Therefore, the piping or resin screw 207 can be removed at this point, allowing the subsequent heat curing process to proceed.

[0153] (ii) Thermal curing (film forming process)

[0154] After applying the hydrophilic film coating liquid, thermal curing is performed to form a film. Furthermore, before thermal curing and before removing the pipe or resin screw 207, it is best to remove excess hydrophilic film coating liquid adhering to the inner surface 203a. This can be done by bringing an absorbent article such as paper into contact with the hydrophilic film coating liquid.

[0155] During heat curing, heating must be performed below the heatproof temperature to prevent deformation of the material of the connection container 203. Since deformation at temperatures above 70°C is a concern for acrylic, heating is performed at 60°C to provide a margin. Since deformation at temperatures above 120°C is a concern for polycarbonate, heating is performed at 100°C to provide a margin.

[0156] Since higher heating temperatures accelerate thermal curing, the higher the heat resistance of substrate 301, the shorter the time required for thermal curing. When using acrylic, which has a lower heat resistance, for one hour at 60°C, a hydrophilic film 305 with a pencil hardness of about B is obtained. After being placed in a high humidity environment with a relative humidity of approximately 70-90% for approximately one hour and then heated at 60°C for another hour, a hydrophilic film 305 with a pencil hardness of about HB is obtained. Once again, being placed in a high humidity environment with a relative humidity of approximately 70-90% for approximately one hour and then heated at 60°C for another hour, a hydrophilic film 305 with a pencil hardness of about H is obtained. Since the acrylic used in substrate 301 has a pencil hardness of about H, curing to this point results in a hydrophilic film 305 with a hardness comparable to that of substrate 301, a level considered sufficient for practical use.

[0157] The reason for adding the step of standing in a high-humidity environment is as follows. Since the thermal curing reaction of the hydrophilic film coating liquid is a hydrolysis reaction, supplying moisture during the reaction is effective. However, in a 60°C thermostat, the amount of moisture in the air is extremely low, making it impossible to supply moisture from the air. Therefore, by interrupting the thermal curing process and standing in a high-humidity environment, moisture in the air adheres to and is absorbed by the hydrophilic film 305 during the thermal curing process, allowing the thermal curing reaction to proceed efficiently when heated again.

[0158] As described above, the film forming method of the pressure sensor cell 112 of this embodiment can form a hydrophilic film 305 comprising, or composed of, at least one of silica particles 302 and alumina particles and a silicon compound on the inner surface 203a of the pressure sensor cell 112. Furthermore, when the film is formed in this manner, the relationship between the arithmetic mean roughness Ra0 of the substrate 301 forming the inner surface 203a and the arithmetic mean roughness Ra1 of the inner surface 203a after the hydrophilic film 305 is formed is 0.8 × Ra0 ≤ Ra1. Therefore, the pressure sensor cell 112 obtained by this film forming method can pump and discharge liquid without retaining bubbles inside.

[0159] f) Automatic analysis method

[0160] The automatic analysis method of this embodiment utilizes nozzles (dispensing nozzles 102, 115, sample dispensing nozzle 10, reagent dispensing nozzle 11) connected to the dispensing mechanism 100, 114 equipped with the above-mentioned pressure sensor unit 112 to suck / eject liquid. As described above, the pressure sensor unit 112 used in the automatic analysis method of this embodiment has a hydrophilic film 305 formed on the inner surface 203a, which is composed of at least one of silica particles 302 and alumina particles and a silicon compound, or is composed of at least one of silica particles 302 and alumina particles and a silicon compound. Moreover, the relationship between the arithmetic average roughness Ra0 of the substrate 301 of the above-mentioned inner surface 203a and the arithmetic average roughness Ra1 of the inner surface 203a after the above-mentioned hydrophilic film 305 is formed is 0.8×Ra0≤Ra1. In this way, since the automatic analysis method uses the above-mentioned pressure sensor unit 112, it is possible to suck / eject liquid without leaving bubbles inside.

[0161] Next, the present invention will be described with reference to examples. However, the present invention is not limited to these examples.

[0162] Example 1

[0163] (1) Preparation of coating liquid for forming a hydrophilic film

[0164] Silica particles (15 g) with an average particle size of 10 nm, diethylene glycol monoacetate (0.5 g) as a dispersant, and ethanol (84.5 g) as a solvent were placed in a 200 ml polypropylene bottle and stirred with an overhead stirrer to prepare 100 g of a 15% by mass silica particle dispersion A.

[0165] 750 g of a silica sol solution B prepared in which the solvent was ethanol and the solid content concentration after hydrolysis was 2% by mass was prepared.

[0166] Dispersion A (1.0 g), silica sol solution B (7.5 g) and ethanol (21.5 g) were added to a polypropylene bottle with a content of 1000 ml. After the bottle was sealed, the mixture was stirred several times to prepare a coating liquid (hydrophilic film coating liquid CS1) (30 g) for forming a hydrophilic film 305 with a solid content of 1.0 mass% and silica particles accounting for 50 mass% of the solid content.

[0167] Furthermore, the contact angle of the hydrophilic film 305 formed on an acrylic plate having an Ra of 10 nm using the hydrophilic film coating liquid CS1 prepared in this example with water was 10°.

[0168] (2) Step of forming the hydrophilic film 305 on the connection container 203 of the pressure sensor unit 112

[0169] Reference Figures 13A to 13C This process will be described.

[0170] Figures 13A to 13C Each of the figures is an explanatory diagram for explaining the process of forming a hydrophilic film on the inner surface of the connection container. Figure 13A Shows the state before coating. Figure 13B The state in which the O-ring 204 is mounted after coating and heat curing is shown. Figure 13C The state in which the pressure sensor 202 is provided, that is, the state of the pressure sensor unit 112 is shown.

[0171] like Figure 13A As shown, the connection container 203 of the pressure sensor unit 112 used in this embodiment is placed on a flat table with the conical apex facing downward. The Ra of the inner surface 203a of the connection container 203 is 100 nm. To prevent the hydrophilic film coating liquid CS1 from adhering to the connection portions 205 and 206 of the connection container 203, suitable resin screws 207 are pre-threaded into the connection portions 205 and 206. In this state, the hydrophilic film coating liquid CS1 is applied to the inner surface 203a of the connection container 203 using a dropper or the like.

[0172] Afterwards, the connected container 203 is flipped so that the conical apex is facing upward, and a piece of paper that has absorbed the excess hydrophilic film coating liquid CS1 is placed on it and allowed to stand. Approximately 10 minutes later, the connected container 203 is placed in a thermostatic bath set at 60°C and left there for one hour. The connected container 203 is then placed in a thermostatic bath controlled at 25°C and 80% humidity and left there for one hour. The connected container 203 is again placed in a thermostatic bath controlled at 60°C and left there for one hour. The connected container 203 is then placed in a thermostatic bath controlled at 25°C and 80% humidity and left there for one hour. Finally, the connected container 203 is once again placed in a thermostatic bath controlled at 60°C and left there for one hour. This forms the desired hydrophilic film 305 on the inner surface 203a of the connected container 203.

[0173] Then, if Figure 13B As shown, the resin screws 207 are removed from the connection parts 205 and 206 , and the O-ring 204 is attached along the peripheral edge of the conical bottom surface of the connection container 203 .

[0174] Then, if Figure 13C As shown, the pressure sensor 202 is placed with the diaphragm 201 facing the inner surface 203a of the connection container 203, completing the pressure sensor unit 112.

[0175] (3) Process of forming a hydrophilic film on an O-ring

[0176] The O-ring 204 used above has the function of sealing the gap between the inner surface 203a of the connection container 203 and the pressure sensor 202, preventing the high-pressure system water 106 from leaking out. Therefore, although it is rare, it may come into contact with the system water 106. Therefore, even if a hydrophilic film 305 is formed on the inner surface 203a of the connection container 203, there is a possibility that air bubbles will adhere to the O-ring 204. Therefore, it is desirable to also form a hydrophilic film 305 on the surface of the O-ring 204.

[0177] Therefore, an amount of the hydrophilic film coating liquid CS1 sufficient to completely immerse the O-ring 204 was placed in a container, and the O-ring 204 was immersed therein for 10 seconds. The O-ring 204 was then lifted with tweezers and heated at 60°C for one hour, similar to the connection container 203. The container was then left in an environment at 25°C and 80% humidity for one hour. After repeating this process twice, the container was heated at 60°C for one hour, thereby producing an O-ring 204 having a hydrophilic film 305 formed on its surface.

[0178] Then, as described above, the O-ring 204 is attached to the connection container 203 having the hydrophilic film 305 formed on the inner surface 203 a , and then the pressure sensor 202 is attached to complete the pressure sensor unit 112 of this embodiment.

[0179] (4) Confirmation of the effect of hydrophilic film formation

[0180] The pressure sensor unit 112 manufactured through the above steps (1) to (3) is mounted on Figure 3 The dispensing mechanism 100 shown is placed in Figure 1 The reagent dispensing and sample dispensing operations were performed using the automatic analyzer 1. As a result, no bubbles were visually confirmed in the connection container 203 of the pressure sensor unit 112, and the dispensing error was also below the standard.

[0181] In contrast, reagent and sample dispensing were performed using a pressure sensor unit 112 without the hydrophilic film 305 formed thereon. As a result, several bubbles were observed within the connection container 203 of the pressure sensor unit 112, and bubbles were also observed adhering to the O-ring 204. The dispensing error exceeded the standard.

[0182] In summary, it was confirmed that the use of the pressure sensor unit 112 in which the hydrophilic film 305 is formed between the connection container 203 and the O-ring 204 can realize the automatic analyzer 1 capable of performing highly accurate dispensing operations.

[0183] Furthermore, the pressure sensor unit 112 manufactured through the above steps was disassembled and the connection container 203 was recovered. In order to obtain the Ra of the inner surface 203a, Figure 14 The vertical surface cutting part 208 and the inclined surface cutting part 209 are cut to prepare the vertical surface roughness measuring part 210 and the inclined surface roughness measuring part 211. Figure 14 This is an explanatory diagram showing a cut portion when measuring the surface roughness of the inner surface of a connection container.

[0184] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the Ra was 90 to 95 nm at the vertical surface roughness measurement site 210, and 86 to 91 nm at the inclined surface roughness measurement site 211. In other words, the Ra after the formation of the hydrophilic film 305 was determined to be at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0185] The cross-section was observed and photographed using an SEM, and the resulting image was used to measure the thickness of the hydrophilic film 305 formed on the connection container 203. The results showed that the roughness measurement site 210 on the vertical surface was 120 to 150 nm, and the roughness measurement site 211 on the inclined surface was 170 to 200 nm.

[0186] Example 2

[0187] The 15 mass % silica particle dispersion A prepared in Example 1 was changed from 1.0 g to 0.6 g, the silica sol solution B was changed from 7.5 g to 10.5 g, and the ethanol was changed from 21.5 g to 18.9 g, and placed in a polypropylene bottle having a content of 1000 ml. After the bottle was sealed and stirred several times, a coating liquid (hydrophilic membrane coating liquid CS2) (30 g) was prepared for forming a hydrophilic membrane 305 having a solid content of 1.0 mass % and silica particles accounting for 30 mass % of the solid content.

[0188] A pressure sensor unit 112 was produced experimentally using the same procedures as in Example 1, except that the hydrophilic film coating liquid CS2 described above was used instead of the hydrophilic film coating liquid CS1. This was then placed in the automatic analyzer 1, and reagent and sample dispensing operations were performed. As a result, no bubbles were visually observed within the connection container 203 of the pressure sensor unit 112, and the dispensing error was also below the standard.

[0189] The pressure sensor unit 112 manufactured through the above steps is disassembled to recover the connection container 203. To determine Ra of the inner surface 203a, a vertical surface roughness measurement site 210 and an inclined surface roughness measurement site 211 are prepared as in Example 1.

[0190] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the Ra was 95 to 97 nm at the vertical surface roughness measurement site 210, and 90 to 95 nm at the inclined surface roughness measurement site 211. In other words, the Ra after the formation of the hydrophilic film 305 was confirmed to be at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0191] Furthermore, when the thickness of the hydrophilic film 305 formed on the connection container 203 was measured in the same manner as in Example 1, it was 100 to 120 nm at the roughness measurement site 210 on the vertical surface and 130 to 150 nm at the roughness measurement site 211 on the inclined surface.

[0192] Example 3

[0193] The 15 mass % silica particle dispersion A prepared in Example 1 was changed from 1.0 g to 1.2 g, the silica sol solution B was changed from 7.5 g to 6.0 g, and the ethanol was changed from 21.5 g to 22.8 g, and placed in a polypropylene bottle with a content of 1000 ml. After the bottle was sealed and stirred several times, a coating liquid (hydrophilic membrane coating liquid CS3) (30 g) was prepared for forming a hydrophilic membrane 305 having a solid content of 1.0 mass % and silica particles accounting for 60 mass % of the solid content.

[0194] A pressure sensor unit 112 was produced experimentally using the same procedures as in Example 1, except that the hydrophilic film coating liquid CS3 described above was used instead of the hydrophilic film coating liquid CS1. This was then placed in the automatic analyzer 1, and reagent and sample dispensing operations were performed. As a result, no bubbles were visually observed within the connection container 203 of the pressure sensor unit 112, and the dispensing error was also below the standard.

[0195] The pressure sensor unit 112 manufactured through the above steps is disassembled to recover the connection container 203. To determine Ra of the inner surface 203a, a vertical surface roughness measurement site 210 and an inclined surface roughness measurement site 211 are prepared as in Example 1.

[0196] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the roughness Ra was 90 to 92 nm at the vertical surface roughness measurement site 210, and 82 to 88 nm at the inclined surface roughness measurement site 211. In other words, it was confirmed that the Ra after the formation of the hydrophilic film 305 was at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0197] Furthermore, when the thickness of the hydrophilic film 305 formed on the connection container 203 was measured in the same manner as in Example 1, it was 140 to 180 nm at the roughness measurement site 210 on the vertical surface and 200 to 230 nm at the roughness measurement site 211 on the inclined surface.

[0198] Example 4

[0199] A pressure sensor unit 112 was produced experimentally using the same procedures as in Example 1, except that silica particles (15 g) with an average particle size of 10 nm were replaced with silica particles (15 g) with an average particle size of 20 nm. The unit was then placed in the automated analyzer 1 and reagent and sample dispensing operations were performed. No bubbles were visually observed within the connection container 203 of the pressure sensor unit 112, and the dispensing error was below the standard.

[0200] The pressure sensor unit 112 manufactured through the above steps is disassembled to recover the connection container 203. To determine Ra of the inner surface 203a, a vertical surface roughness measurement site 210 and an inclined surface roughness measurement site 211 are prepared as in Example 1.

[0201] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the roughness Ra was 86 to 90 nm at the vertical surface roughness measurement site 210, and 82 to 84 nm at the inclined surface roughness measurement site 211. In other words, it was confirmed that the Ra after the formation of the hydrophilic film 305 was at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0202] Furthermore, when the thickness of the hydrophilic film 305 formed on the connection container 203 was measured in the same manner as in Example 1, it was 160 to 200 nm at the roughness measurement site 210 on the vertical surface and 200 to 240 nm at the roughness measurement site 211 on the inclined surface.

[0203] Example 5

[0204] A pressure sensor unit 112 was produced experimentally using the same procedures as in Example 1, except that the silica particles (15 g) with an average particle size of 10 nm were replaced with alumina particles (15 g) with an average particle size of 20 nm. The unit was then placed in the automated analyzer 1 and reagent and sample dispensing operations were performed. Visual inspection revealed no air bubbles within the connection container 203 of the pressure sensor unit 112, and the dispensing error was below the standard.

[0205] The pressure sensor unit 112 manufactured through the above steps is disassembled to recover the connection container 203. To determine Ra of the inner surface 203a, a vertical surface roughness measurement site 210 and an inclined surface roughness measurement site 211 are prepared as in Example 1.

[0206] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the roughness Ra was 86 to 90 nm at the vertical surface roughness measurement site 210, and 82 to 84 nm at the inclined surface roughness measurement site 211. In other words, it was confirmed that the Ra after the formation of the hydrophilic film 305 was at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0207] Furthermore, when the thickness of the hydrophilic film 305 formed on the connection container 203 was measured in the same manner as in Example 1, it was 160 to 200 nm at the roughness measurement site 210 on the vertical surface and 200 to 240 nm at the roughness measurement site 211 on the inclined surface.

[0208] Example 6

[0209] A pressure sensor unit 112 was produced experimentally using the same procedures as in Example 1, except that silica particles (15 g) with an average particle size of 10 nm were replaced with silica particles (15 g) with an average particle size of 40 nm. The unit was then placed in the automated analyzer 1 and reagent and sample dispensing operations were performed. The results showed that the dispensing error, measured as a mass ratio of the dispensed amount, was 1 / 100 to 5 / 100 for both reagent and sample dispensing.

[0210] Since the particles used had a large diameter, the hydrophilicity of the hydrophilic membrane 305 decreased, and the dispensing error increased slightly, but the dispensing error was below the standard. Furthermore, no bubbles were visually observed in the connection container 203 of the pressure sensor unit 112.

[0211] The pressure sensor unit 112 manufactured through the above steps is disassembled to recover the connection container 203. To determine Ra of the inner surface 203a, a vertical surface roughness measurement site 210 and an inclined surface roughness measurement site 211 are prepared as in Example 1.

[0212] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the roughness Ra was 84 to 86 nm at the vertical surface roughness measurement site 210, and 80 to 82 nm at the inclined surface roughness measurement site 211. In other words, it was confirmed that the Ra after the formation of the hydrophilic film 305 was at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0213] Furthermore, when the thickness of the hydrophilic film 305 formed on the connection container 203 was measured in the same manner as in Example 1, it was 180 to 220 nm at the roughness measurement site 210 on the vertical surface and 250 to 300 nm at the roughness measurement site 211 on the inclined surface.

[0214] Example 7

[0215] The 15 mass % silica particle dispersion A prepared in Example 1 was changed from 1.0 g to 1.3 g, the silica sol solution B was changed from 7.5 g to 5.25 g, and the ethanol was changed from 21.5 g to 23.45 g. The mixture was placed in a polypropylene bottle having an internal capacity of 1000 ml. The bottle was sealed and stirred several times to prepare a coating liquid (hydrophilic film coating liquid CS4) (30 g) for forming a hydrophilic film having a solid content of 1.0 mass % and silica particles accounting for 65 mass % of the solid content.

[0216] A pressure sensor unit 112 was prototyped using the same procedures as in Example 1, except that the hydrophilic film coating liquid CS4 described above was used instead of the hydrophilic film coating liquid CS1. The pressure sensor unit 112 was then placed in the automatic analyzer 1 and reagent and sample dispensing operations were performed. As a result, no bubbles were visually observed within the connection container 203 of the pressure sensor unit 112.

[0217] Since the addition rate of the particles used was high, the hydrophilicity of the hydrophilic film 305 became lower, and the error in dispensing became slightly larger, but the error in dispensing was below the standard.

[0218] The pressure sensor unit 112 manufactured through the above steps is disassembled to recover the connection container 203. To determine Ra of the inner surface 203a, a vertical surface roughness measurement site 210 and an inclined surface roughness measurement site 211 are prepared as in Example 1.

[0219] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the roughness R of the vertical surface at the roughness measurement site 210 was 88 to 90 nm, and the roughness R of the inclined surface at the roughness measurement site 211 was 80 to 84 nm. In other words, the Ra after the formation of the hydrophilic film 305 was confirmed to be at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0220] Furthermore, when the thickness of the hydrophilic film 305 formed on the connection container 203 was measured in the same manner as in Example 1, it was 160 to 200 nm at the roughness measurement site 210 on the vertical surface and 220 to 250 nm at the roughness measurement site 211 on the inclined surface.

[0221] Example 8

[0222] The 15 mass % silica particle dispersion A prepared in Example 1 was changed from 1.0 g to 0.5 g, the silica sol solution B was changed from 7.5 g to 11.25 g, and the ethanol was changed from 21.5 g to 18.25 g, and placed in a polypropylene bottle having a content of 1000 ml. After the bottle was sealed and stirred several times, a coating liquid (hydrophilic membrane coating liquid CS5) (30 g) was prepared for forming a hydrophilic membrane 305 having a solid content of 1.0 mass % and silica particles accounting for 25 mass % of the solid content.

[0223] A pressure sensor unit 112 was prototyped using the same procedures as in Example 1, except that the hydrophilic membrane coating liquid CS5 described above was used instead of the hydrophilic membrane coating liquid CS1. This pressure sensor unit 112 was then installed in the automated analyzer 1, and reagent and sample dispensing operations were performed. The results showed that the dispensing error was 3 / 100 to 5 / 100 of the amount dispensed in both reagent and sample dispensing.

[0224] Since the addition rate of the particles used was low, the hydrophilicity of the hydrophilic membrane 305 decreased, and the dispensing error increased slightly, but the dispensing error was below the standard. Furthermore, no bubbles were visually confirmed in the connection container 203 of the pressure sensor unit 112.

[0225] The pressure sensor unit 112 manufactured through the above steps is disassembled to recover the connection container 203. To determine Ra of the inner surface 203a, a vertical surface roughness measurement site 210 and an inclined surface roughness measurement site 211 are prepared as in Example 1.

[0226] When the surface corresponding to the inner surface 203a of the connection container 203 was measured, the roughness Ra was 92 to 97 nm at the vertical surface roughness measurement site 210, and 88 to 93 nm at the inclined surface roughness measurement site 211. In other words, the Ra after the formation of the hydrophilic film 305 was confirmed to be at least 0.8 times the Ra (100 nm) before the formation of the hydrophilic film 305.

[0227] Furthermore, when the thickness of the hydrophilic film 305 formed on the connection container 203 was measured in the same manner as in Example 1, it was 100 to 120 nm at the roughness measurement site 210 on the vertical surface and 140 to 170 nm at the roughness measurement site 211 on the inclined surface.

[0228] Conventional pressure sensor units have difficulty accurately measuring pressure due to bubbles adhering to their inner surfaces. However, in this case, as shown in Examples 1 to 8, a suitable hydrophilic film 305 is provided on the inner surface 203a of the connection container 203. The relationship between the arithmetic mean roughness Ra0 of the substrate 301 forming the inner surface 203a and the arithmetic mean roughness Ra1 of the inner surface 203a after the hydrophilic film 305 is formed is 0.8 × Ra0 ≤ Ra1, achieving bubble-free operation. Furthermore, this enables the automatic analyzer 1 equipped with the pressure sensor unit 112 to accurately measure pressure, confirming that accurate dispensing is possible using the dispensing mechanism 100.

[0229] The above embodiments and examples have been used to describe in detail the automatic analysis device 1, the automatic analysis method, and the film forming method of the pressure sensor unit 112 of the present invention. However, the present invention is not limited to the above embodiments and examples, and includes various modifications. For example, in order to easily explain the present invention, the above embodiments have been described in detail, but it is not necessarily limited to having all the structures described. In addition, a part of the structure of a certain embodiment can be replaced with the structure of another embodiment, and the structure of another embodiment can be added to the structure of a certain embodiment. In addition, it is possible to add, delete, or replace a part of the structure of each embodiment with another structure.

[0230] Explanation of symbols

[0231] 1—Automatic analyzer, 2—Reagent container, 3—Reagent container filling unit, 4—Reagent cooling box, 5—Sample container, 6—Stand, 7—Stand transport line, 8—Reaction container, 9—Cultivation plate, 10—Sample dispensing nozzle, 11—Reagent dispensing nozzle, 12—Reaction container transport mechanism, 13—Sample dispensing position, 14—Sample dispensing head / Reaction container transport mechanism, 15—Sample dispensing head / Reaction container holding component, 16—Reaction container stirring mechanism, 17—Sample dispensing head / Reaction container disposal hole, 18—Sample dispensing head assembly position, 19—Lid, 20—Reagent suction hole, 21—Detection unit, 22—Automatic analyzer, 23—Sample dispensing nozzle, 24—Reagent dispensing nozzle, 25—Nozzle cleaning mechanism, 26—Measurement unit, 100—Dispensing mechanism, 101—Pipette tip, 102—Dispensing nozzle, 103—Control unit, 104—Flow path, 105— Syringe, 106 - system water, 107 - cylinder, 108 - plunger, 109 - water supply tank, 110 - solenoid valve, 111 - water supply pump, 112 - pressure sensor unit, 113 - pressure sensor, 114 - dispensing mechanism, 115 - dispensing nozzle, 116 - cleaning water, 117 - nozzle cleaning mechanism, 118 - flow path, 201 - diaphragm, 202 - pressure sensor, 203 - connection container, 203a - inner surface, 204—O-ring, 205—connecting portion, 205a—inflow and outflow port, 206—connecting portion, 206a—inflow and outflow port, 208—vertical surface cutting portion, 209—inclined surface cutting portion, 210—vertical surface roughness measurement portion, 211—inclined surface roughness measurement portion, 301—substrate, 302—silica particles, 303—voids, 304—silica adhesive, 305—hydrophilic film.

Claims

1. An automatic analysis device, characterized in that A dispensing mechanism includes a nozzle for sucking / discharging liquid, a pressure generating mechanism connected to the nozzle and generating pressure for sucking / discharging the liquid, and a pressure sensor unit for measuring the pressure in the flow path including the nozzle and the pressure generating mechanism. A hydrophilic film including at least one of silica particles and alumina particles and a silicon compound is formed on the inner surface of the pressure sensor unit. The relationship between the arithmetic mean roughness Ra0 of the substrate on the inner surface and the arithmetic mean roughness Ra1 of the inner surface after the hydrophilic film is formed is 0.8×Ra0≤Ra1.

2. The automatic analysis device according to claim 1, characterized in that When the cross-sectional area of ​​each of the liquid inflow and outflow ports of the pressure sensor unit is denoted by α and the area of ​​the pressure receiving surface of the pressure sensor unit is denoted by β, α<β.

3. The automatic analysis device according to claim 1, characterized in that The inner surface of the pressure sensor unit is in the shape of a cone. The cone is arranged so that its apex is vertically upward. A liquid inlet and outlet connected to the pressure generating mechanism is provided in the tangential direction of the bottom circumference of the cone. The apex portion is provided with a liquid inlet and outlet connected to the nozzle. The pressure receiving surface of the pressure sensor unit is arranged on the bottom surface of the cone.

4. The automatic analysis device according to claim 1, characterized in that The average particle size of the silica particles and the alumina particles is 10 to 20 nm.

5. The automatic analysis device according to claim 1, characterized in that The ratio of the silica particles and the alumina particles is 30 to 60% by mass.

6. The automatic analysis device according to claim 1, characterized in that An O-ring is interposed between the pressure sensor of the pressure sensor unit and a connection container serving as a housing of the pressure sensor unit, and the hydrophilic film is formed on a surface of the O-ring.

7. The automatic analysis device according to claim 3, characterized in that The hydrophilic film is not formed on a surface of the inflow / outlet that contacts the flow path.

8. The automatic analysis device according to claim 1, characterized in that The hydrophilic film has a thickness of 50 nm or more.

9. The automatic analysis device according to claim 1, characterized in that The hydrophilic film has an arithmetic mean roughness of 0.08 μm or more.

10. An automatic analysis method, characterized in that Liquid is sucked / discharged using a nozzle connected to a dispensing mechanism equipped with a pressure sensor unit. The pressure sensor unit has a hydrophilic film formed on its inner surface, which is composed of at least one of silica particles and alumina particles and a silicon compound. The relationship between the arithmetic average roughness Ra0 of the substrate of the inner surface and the arithmetic average roughness Ra1 of the inner surface after the hydrophilic film is formed is 0.8×Ra0≤Ra1.

11. A method for forming a film of a pressure sensor unit, characterized in that: have: a screwing step in which threaded components are screwed into all inflow and outflow ports of the pressure sensor unit; a coating step of coating the inner surface of the pressure sensor unit in which the threaded member is screwed into the inlet and outlet with a hydrophilic film coating liquid containing at least one of silica particles and alumina particles and a silicon compound; and a film-forming step in which the hydrophilic film coating liquid applied to the inner surface is heated to form a hydrophilic film; The relationship between the arithmetic mean roughness Ra0 of the substrate on the inner surface and the arithmetic mean roughness Ra1 of the inner surface after the hydrophilic film is formed is 0.8×Ra0≤Ra1.

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