JP3407068B2 - Chemical analyzer - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a chemical analyzer for quantifying the concentration of a substance dissolved in a liquid, and more particularly to a chemical analyzer for analyzing components such as biological fluid and water.

[0002]

2. Description of the Related Art As a conventional chemical analyzer, there is a chemical analyzer described in U.S. Pat. No. 4,451,433. This device consists of a colorimetric measurement unit for analyzing and quantifying proteins, enzymes, and urine components in blood, and an ion analysis unit for analyzing ions in blood. Therefore, a large-scale device has a processing speed of 9000 tests or more.

There are dozens of colorimetric measurement items of the chemical analyzer represented by the above-mentioned prior art, and at least about 10 items are analyzed for one sample even in the usual inspection items. In order to perform these items with one device, a mechanism is provided in which a reagent is selected from a plurality of reagent containers and sequentially supplied to the reaction container in a predetermined reagent amount. In the case of the above conventional technique, a system called a reagent pipetting mechanism is adopted as the supply mechanism. The reagent pipetting mechanism mainly includes a nozzle that sucks and holds the reagent inside, a mechanism that moves the nozzle three-dimensionally, and a suction-discharge control pump that sucks and discharges the sample into the nozzle. In order to transmit the suction / discharge operation of the pump to the nozzle with good response, the pipe line between the pump and the nozzle is filled with pure water. However, in order to avoid mixing of the pure water and the reagent, the space between them is separated by air. This air layer is formed by sucking air into the nozzle before sucking the reagent. Reagent supply is performed as follows.
First, the nozzle is immersed in the reagent container by the three-dimensional moving mechanism, and a predetermined amount of reagent is sucked inside. After that, the reagent container is separated and moved to the upper part of the reaction container, and the reagent inside the nozzle is discharged. After the reagent is discharged, the inside and outside of the nozzle is flushed with the cleaning liquid in the nozzle cleaning tank in order to avoid contamination of the next reagent. Since the trajectory of the nozzle of the reagent pipetting mechanism moves is fixed, a reagent container moving mechanism for positioning the reagent container is provided below the moving path. This reagent supply mechanism has a limit in the number of tests per unit time because it takes a relatively long time to move the nozzle three-dimensionally and to wash it, but it is a system suitable for analyzing a relatively large number of items. Is.

Another reagent supply mechanism is a dispenser mechanism including a syringe pump, a flow path switching valve and a reagent discharge nozzle. Tubes are collected from each reagent container in the flow path switching valve. Also, the same number of tubes extend from the same valve to each reagent discharge nozzle. Further, a single tube is connected from the flow path switching valve to a syringe pump for controlling the flow of the reagent. First, as an initial state, the tubes from the reagent container to the switching valve and from the switching valve to the reagent discharge nozzle are filled with each reagent.
In this state, when it is desired to discharge a desired reagent, the switching valve operates and the tube extending from the corresponding reagent container and the syringe pump are connected. The syringe pump performs a suction operation and draws a predetermined amount of reagent into the tube on the syringe pump side through the switching valve. Next, the switching valve operates,
Connect the tube from the syringe pump to the switching valve and the tube connecting the switching valve to the reagent discharge nozzle. In this state, the syringe pump discharges to discharge a predetermined amount of the reagent in the tube into the reaction container. With this method, switching and supply of reagents can be performed at high speed. In addition, there are only reagent types for reagent ejection nozzles, and there is no need to clean the inside of the tube following the nozzle. However, since it is necessary to provide a reagent discharge nozzle for each type of reagent, this is not suitable when there are many types of reagents to be used. Rather, it is suitable when analyzing items with few types but many tests.

As another conventional technique, Japanese Patent Laid-Open No. 63-131
There are 066 automatic analyzers. The first purpose of this is to miniaturize the apparatus by overlapping the movement locus of the reaction container folder holding the reaction container with the movement locus of the reagent container folder holding the reagent container. The reagent is discharged by a piston integrally formed on the side surface of each reagent container. The piston is driven by a piston rod driving device provided at the reagent discharge position. At the dispensing position, the piston rod drive of the reagent container is temporarily connected. Next, the piston rod is pulled upward, and the reagent in the reagent container is sucked into the piston. At the stage of reaching the uppermost part, it meshes with the gear that rotates the piston, and the gear rotates the piston 180 degrees. At that time, the hole that was opened for suction is closed by the rotation of the piston, and the hole that is connected to the discharge port is opened on the contrary.
When the piston rod moves downward, the reagent in the piston is discharged into the reaction container through the hole.

On the other hand, in Japanese Unexamined Patent Publication (Kokai) No. 7-60972, the nozzle of an ink jet head is formed integrally with a flow path substrate made of ABS resin, the nozzle surface is made highly water repellent, and the flow path inside the nozzle is made hydrophilic to make ink It describes a method of manufacturing an inexpensive ink jet head that improves ejection force and reduces the number of parts.

[0007]

The above-mentioned conventional reagent supply mechanism has the following problems.

The reagent pipetting mechanism has the following three problems. First of all, there is a waste of reagent amount. That is, an air layer is provided between the reagent sucked into the nozzle so as not to mix with the pure water, but the pure water still mixes with the upper portion of the reagent along the inner wall of the nozzle. Therefore, in order to prevent the mixed reagents from being used in the analysis, the reagent is sucked into the nozzle about 30% more than the actual amount of the reagent required for the analysis. The reagents used for this analysis are very expensive, and therefore, this excess amount of reagents leads to a waste of inspection costs. The second is that cleaning requires a large amount of time and a large amount of liquid. That is, in order to avoid mixing of the reagents with each other through the nozzle, the inside and outside of the nozzle are washed with the washing liquid every time, but the amount of the washing liquid and the washing time for that are required. Furthermore the third
The problem is that even if the inside and outside of the nozzle are washed with the washing liquid, some residue remains, which causes an error in the measured value.

The reagent dispenser mechanism has the following two problems. First of all, similarly to the above, a wasteful amount of reagent is generated. In order to expel the reagent quickly to any reagent, it is necessary to fill all the reagents in the tube from the reagent container to the switching valve and the tube from the switching valve to the ejection nozzle before starting the analysis in advance. There is. The reagent filled in this portion is wastefully discarded when the apparatus is stopped. Depending on the type of reagent and the total length of the tube, reagents equivalent to 100 or more may be wastefully discarded. The second problem is
The maintenance of the switching valve is a troublesome point. That is, different reagents pass through the switching valve one after another, and become gradually dirty. If different reagents touch each other, the valve seat may stick. Therefore, it is necessary to disassemble and clean the switching valve regularly.

Further, in the piston system which is the third example,
The amount of wasteful reagent is small compared to any of the above examples,
However, since there is a flow path from the reagent container to the tip of the pipettor when the apparatus is shut down, the reagent remains and this portion is wastefully discarded. The amount of reagent supplied must be changed according to the concentration of the sample, but the amount of reciprocating motion of the piston is predetermined because the position of the gear on the top of the piston for rotating is fixed. It is possible to discharge only the reagent amount. Further, since the piston is provided on the side surface, it is necessary to temporarily pump up the reagent to a position higher than the position of the reagent container. Also, the pressure loss due to the flow path from the reagent container to the tip of the pipettor cannot be ignored. For these reasons, it is necessary to apply a certain amount of pressure, which complicates and enlarges the piston drive mechanism. That is, it hinders the use of a simple and small pump.

As described above, the conventional reagent supply method has a problem in that there is a waste of reagent amount in any method. Further, the reagent pipetting mechanism requires a large amount of washing liquid to prevent mutual contamination between reagents. The reagent dispenser mechanism requires regular troublesome disassembly and cleaning. Further, the piston method can supply only a predetermined volume of reagent. Or the structure is complicated.

In order to solve the above problems, it is necessary to improve the dropping method of the reagent, the structure of the pump, the structure of the analyzer and the like, and at the same time improve the liquid drainage property at the time of dropping the reagent, and It is necessary to improve controllability. For that purpose, it is important to improve the structure of the nozzle and the liquid drainage function. Japanese Patent Laid-Open No. 7-6097 relating to improvement of nozzle function
2 acrylonitrile butadiene styrene (A
BS) substrates and water-repellent coatings have low chemical resistance and are good for inks as fluids, but have problems when used for chemical analysis such as ejection of acidic or basic reagents.

Therefore, an object of the present invention is that the reagents are not wasted, the cleaning liquid is hardly required, and the periodical disintegration cleaning is not required, so that the trace amount of the supplied reagent can be easily controlled.
It is an object of the present invention to provide a chemical analysis device having a simple nozzle, a high ejection resolution and ejection stability, and a chemical resistant nozzle.

[0014]

In order to achieve the above object, the chemical analyzer of the present invention comprises a reaction container holder for holding a plurality of reaction containers for containing samples, and various kinds of samples to be added to the samples in the reaction containers. A plurality of reagent containers that contain reagents one by one, a pump that is attached to the bottom of the reagent container and that inhales a prescribed amount of reagent and injects it dropwise into the reaction container, and a measurement that measures the physical properties of the sample after the reagents are added. In the device provided with the device, the pump includes a silicon pump body, a silicon nozzle joined to the front surface of the pump body, and having a plate-like shape and a discharge hole that is connected to the outlet of the pump body at the center of the plate. And a chemical resistant layer having corrosion resistance to a reagent is formed on the front and back surfaces of the substrate of the nozzle and the inner surface of the ejection hole, and further, the front surface of the substrate, or the front surface of the plate and the inner portion of the ejection hole. A fluororesin layer on the chemical layer, or a compound containing fluorine (e.g. fluorocarbon compounds _{CF 3 (CF 2) m (} CH 2) nSi (OCH 3) 3) , characterized in that has been formed.

The chemical resistant layer is made of silicon dioxide, A
It is preferably made of u, Ag, Pt or a corrosion resistant alloy.
Further, it is preferable that the surface of the fluororesin layer is uneven. Further, it is preferable that the tip of the discharge hole on the substrate of the nozzle be chamfered round.

When the material of the discharge pump and the nozzle is silicon, fine processing becomes possible by using a semiconductor manufacturing process, and mounting on a reagent container is possible. In addition, silicon dioxide, Au, Ag, P on the surface of silicon
By forming a t or alloy layer, the chemical resistance is further improved. Also, if fine irregularities are formed on the nozzle surface,
The surface shape effect makes it easier to repel the reagent. A silicon dioxide layer is also formed on the surface of the discharge pump.

Further, the tip edge portion of the discharge hole of the nozzle is
By making the structure such that the cross section has an arc shape, the thickness of the fluororesin layer is made uniform, and therefore, peeling of the layer that occurs when the fluororesin layer at the edge portion is thin can be prevented.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION An embodiment of a chemical analyzer of the present invention will be described with reference to FIGS. FIG. 1 is an overall configuration diagram of a chemical analyzer equipped with the reagent supply mechanism of the present invention,
2 is a detailed explanatory view of the reagent supply mechanism, FIG. 3 is a plan view of FIG. 2, FIG. 4 is an exploded perspective view of a pump nozzle provided in the reagent supply mechanism according to the present invention, and FIGS. 3 is a cross-sectional view of various nozzles having different configurations. FIG. 9 shows the results of testing the liquid cut-off property and the durability of the nozzle of the present invention and the nozzle of the comparative example. FIG. 10 is a cross-sectional view of the nozzle showing a state of the reagent after the reagent is discharged from the reagent discharge hole of the embodiment, and FIG. 11 is a cross-section of the nozzle when the embodiment of the present invention is not shown. It is a figure. Figure 12
In an enlarged perspective view of a part of the surface of the nozzle according to the present invention,
FIG. 13 is an enlarged perspective view of a part of the surface of another nozzle according to the present invention, and FIG. 14 is an enlarged side view of a part of the surface of another nozzle according to the present invention.

First, the structure of the chemical analyzer of the present invention will be described with reference to FIGS. 1, 2 and 3. FIG. 1 (a) is a plan view of the chemical analyzer 11, and FIG. 1 (b) is a front view thereof. A sample holder 22 for holding a plurality of test tubes 21 containing a sample 20 arranged in a circular shape on a plane is provided on the upper portion of the chemical analyzer 11. A sample pipetter 31 for sucking the sample 22 in the test tube 21 is provided beside the circle where the sample holders 22 are lined up. The sample pipetter 31 sucks a sample from the test tube 21 and holds it inside, a nozzle 32, a three-dimensional drive mechanism 33 that raises and lowers the nozzle 32, and swivels, and sucks or discharges the sample into the nozzle 32. A pump (not shown) is provided. The sample holder 22 is rotationally driven by a rotational drive mechanism 23 in order to position the plurality of test tubes 21 directly below the nozzle 32 of the sample pipetter 31 one by one. Next to the sample holder 22, a reaction disc 42 is placed as if a sample pipetter 31 is sandwiched.
Is installed. The reaction disk 42 holds a plurality of reaction vessels 41 arranged in a circular shape in a plane and sequentially rotates to move the reaction vessels 41 to the other lower position of the nozzle 32 of the sample pipetter 31. There is. The lower half of each reaction container 41 is immersed in a constant temperature bath 43 in which constant temperature water flows. The reaction disk 42 is supported by a reaction disk rotation drive mechanism 44 in order to sequentially move the reaction container to the lowered position of the nozzle 32 of the sample pipetter 31. Above the outer peripheral edge of the reaction disk 42, in addition to the sample pipetter 31, a first reagent supply section 51, a second reagent supply section 61, a reaction container cleaning mechanism 71, and a spectroscopic measurement section 81.
Are provided in order.

Among them, the structure of the reagent supply section 51 will be described in detail with reference to FIGS. 2 and 3. The reagent supply unit 51 is
It is roughly divided into four parts, that is, a plurality of reagent containers 52, a reagent holder 53 holding the reagent containers 52, a micropump 54, and a reagent holder rotation drive mechanism 55. The reagent holder 53 has the reagent container 5 around the central axis 56.
It is structured to hold 2 on the circumference. The same number of membrane pumps 54 as the number of reagent containers 52 held are provided at the bottom of the reagent holder 53. There is a connection hole 521 on the bottom surface of the reagent container 52, and by strongly pressing it toward the bottom of the reagent holder 53, it is connected to the suction hole 541 of the micropump 54. The nozzle 100 is joined to the tip of the micropump 54,
A discharge hole 542 formed in the nozzle 100 is provided vertically downward. Here, the nozzle 100 is
It is a general term for some nozzles described later. On the side surface of the reagent container 52, a magnetic unit 522 in which data describing the type of reagent is written is provided. A magnetic reader 531 for reading the data of the magnetic unit 522 is provided at the corresponding circumferential position of the reagent holder 53.
The signal line from the magnetic reader is connected to the determination unit 57. Further, the determination unit 57 is connected to the micro pump control unit 58. The micro pump 54 is driven by the micro pump controller 58. The reagent holder 53 is configured to be rotationally moved by a reagent holder rotation drive mechanism 55. The second reagent supply unit 61 has the same configuration as the first reagent supply unit 51.

FIG. 4 shows the first and second reagent supply sections 51 and 6
2 is an outline view of a nozzle 100 attached to the first micro pump 54 and the discharge hole 542. FIG. The internal structure of the micropump is not shown. The nozzle 100 has a discharge hole 10
1 (the same as the discharge hole 542) is provided, and the upper portion of the discharge hole 101 connected to the outlet of the main body of the micropump 54 is countersunk. The nozzle 100 shown here has a rectangular plate shape, but may have a disk shape, an elliptical plate shape, or any other shape.

An embodiment of the nozzle attached to the tip of the micropump will be described below. (Embodiment 1) FIG. 5 is a sectional view (section AA in FIG. 4) showing the structure of a nozzle 100A of Embodiment 1. Nozzle 100
A is a nozzle plate 102 made of silicon and having a discharge hole formed in the center of the plate, a silicon dioxide layer 103 forming the surface of the nozzle substrate 102, and the nozzle substrate 102.
And a fluororesin layer 104 formed on the silicon dioxide layer 103 on the lower surface and the inner surface of the discharge hole 101. The material of the nozzle substrate 102, that is, silicon can be processed into a minute and complicated shape by micromachining processing represented by a semiconductor process. The silicon dioxide 103 layer is formed by thermal oxidation to improve the chemical resistance of the nozzle substrate 102. The fluororesin layer 104 imparts water repellency to the lower surface of the nozzle substrate 102 and the inner surface of the ejection hole 101.

Example 2 As in Example 1, a thermally oxidized silicon layer was formed on a silicon nozzle substrate, and then a compound layer containing fluorine was formed. The compound containing fluorine is a fluoroalkylsilane.

(Embodiment 3) The edge portion of the tip of the discharge hole of the silicon nozzle substrate was processed so that the cross section became an arc. Then, as in Example 1, a thermally oxidized silicon layer was formed on the nozzle substrate, and then a fluororesin layer 104 was formed.

(Embodiment 4) FIG. 6 shows a nozzle 1 of Embodiment 4.
It is sectional drawing which shows the structure of 00B. Nozzle substrate 102
Is silicon as in FIG. 5, and thermal oxide silicon 103 was formed on the surface thereof. An Au layer 107 was formed on the thermally oxidized silicon 103. Further, the fluororesin layer 104 was formed on the Au layer 107 on the reagent discharge side of the nozzle. By providing the Au layer 107, the fluororesin layer 10
Even if there is a pinhole in 4 and the reagent penetrates, Au
Has high alkali resistance and acid resistance and does not elute, so that the fluororesin layer 104 is not peeled off. Further, when Au is formed on the surface opposite to the reagent ejection side, this surface is a surface to be bonded to the main body of the micro-micro pump 54, and the presence of Au improves the bonding property. This Au layer 10
7 is not limited to Au and may be any as long as it has high chemical resistance, for example, a superalloy such as Hastelloy, a resin such as polypropylene or a ceramic such as Si ₃ N _4, or Ag or Pt. . Also, the bondability with the main body of the micropump 54 (the bondability in low temperature bonding or diffusion bonding)
It is desirable to use a metal in order to improve.

(Embodiment 5) A nozzle 100C of Embodiment 5 shown in FIG. 7 is the nozzle shown in FIG. 6 in the case where there is no thermally oxidized silicon layer, and an Au layer 107 is formed on a silicon substrate 102, A fluororesin layer 104 was formed on top. As a result, since Au is chemically resistant, the thermally oxidized silicon layer can be eliminated, and the processing steps can be simplified.

(Sixth Embodiment) FIG. 8 shows the nozzle 10 of the sixth embodiment.
It is sectional drawing which shows the structure of 0D. The nozzle 100D is a case where the Au layer 107 is formed on the silicon substrate 102 and the compound 114 containing fluorine is formed on the entire surface of the nozzle. In this case, in order to improve the bondability with the main body of the micropump 54, Au is further formed on the fluororesin layer 114 on the bonding surface.
The layer 115 was formed.

(Embodiment 7) Silicon nozzle substrate 102
On the surface of, the unevenness in the form of a grid shown in FIG. 12 was formed by a micromachine process. Then, the same thermally oxidized silicon layer 103 and fluororesin layer 104 as in Example 1 were formed.

(Embodiment 8) Silicon nozzle substrate 102
The surface of was coated with particles of silicon dioxide having a particle diameter of 120 nm. Then, the same fluororesin layer 104 as in Example 1 was formed.

Comparative Example A silicon dioxide layer was formed on the surface of a silicon nozzle substrate 102 by thermal oxidation.

The silicon dioxide layer formed by thermal oxidation in the above embodiment is not particularly limited to silicon dioxide and may be any compound of silicon which is a substrate material. For example, silicon nitride Si ₃ N ₄ or the like.

The Au layer was formed by sputtering, and the reagent ejection side surface of the nozzle substrate and the opposite surface were sequentially coated. However, if there is an apparatus capable of simultaneously sputtering the two surfaces, the sputtering time can be shortened.

Although silicon was used as the nozzle material because it is easy to carry out a micromachine process, the nozzle material is not limited to silicon and may be alkali-resistant stainless steel (S
It may be a metal material such as US) or a resin such as acid-resistant polytetrafluoroethylene (PTFE).

The fluororesin layer shown in FIGS. 5 to 8 is also formed on the inner wall surface of the discharge hole of the nozzle, but it is essential on the lower surface of the nozzle substrate 102 and is not formed on the inner wall surface of the discharge hole. , Need not be formed. This is a difference in terms of the water repellency of the fluororesin layer, whether the position of the interface between the liquid and air when the liquid runs out is the nozzle tip surface or the inside of the discharge hole.

A reagent discharge test was carried out for each of the nozzles of Examples 1 to 8 and Comparative Example described above, and the reagent cut-off property and the durability of the fluororesin layer or the compound layer containing fluorine were examined.
The ejection test method was performed by measuring the amount of the ejected reagent when the reagent was repeatedly ejected and evaluating the variation. The evaluation result was good when the variation amount of the reagent was within 10% of the ejection amount. When the variation amount of the reagent is 10% or more, the fact that the analysis result of the sample is affected is a constraint condition because the analyzer of the present invention uses the optical measurement. The durability was evaluated by visually observing the wettability of the nozzle after the discharge test and the presence or absence of peeling of the fluororesin layer or the compound layer containing fluorine.

The results of the discharge test are shown in FIG. The ejection performance of each of the nozzles of Examples 1 to 8 is good. The nozzle of the comparative example was defective. The durability of Examples 3 to 8 was good. Examples 1 and 2 and the comparative example were defective.

FIG. 10 is a diagram showing a state where the reagent is discharged from the nozzle and the reagent is about to be interrupted. Since the surface tension of the fluororesin layer or the compound layer 104 containing fluorine is low, the reagent becomes a liquid ball 116. When the size of the liquid ball 116 becomes a certain size, the reagent of the fluororesin layer or the compound layer 104 containing fluorine is Due to the influence of surface tension, it separates from the reagent filling the nozzle holes. For this reason, the reagent is likely to be interrupted, and the stability of the amount of the discharged reagent is improved.

On the other hand, FIG. 11 is a view showing a state of the reagent after the reagent is discharged by the nozzle in which the fluororesin layer or the compound layer containing fluorine is not formed. The reagent 117 is
When the reagent is discharged to the reagent discharge side of the nozzle and then discharged, the wet amount of the reagent is also discharged, and the stability of the amount of the reagent is not good. Moreover, the cutting ability of the reagent is low.

When the nozzle of each of the embodiments described above is used, the variation in the discharge amount of the reagent is within 10%, and the chemical analysis device has a high performance.

It is necessary that the fluororesin layer or the fluorine-containing compound layer is hard to be wet with the reagent. Since the alcohol-based reagent has a lower surface tension than the water-based reagent, the contact angle is low, but when the contact angle is 65 degrees or more, the liquid cut-off property was good.

If the surface of the fluororesin layer or the compound layer containing fluorine is smooth, the contact angle with respect to water is about 100 to 110 degrees. In order to further improve the contact angle, it is preferable to form fine irregularities on the surface of the compound layer containing fluorine. Specifically, when the nozzle substrate is silicon, micromachining is used to form the lattice-shaped protrusions 118 and depressions 119 shown in FIG. 12 or the protrusions 120 and depressions 12 shown in FIG. 13 on the surface of the silicon.
1 was formed, and a fluororesin layer or a fluorine-containing compound layer was coated thereon. The protrusions 118 and 120 and the depressions 119 and 121 may be formed in a cylindrical shape, a conical shape, a pyramidal shape, a prismatic shape, a dendritic shape, a petal shape, or a combination thereof.

If the nozzle substrate is other than silicon, micromachining can be used by coating the nozzle substrate with silicon. In the case of resin,
It is possible to form irregularities on the surface by a dry process such as ion implantation or plasma irradiation. Further, in the case of metal, in addition to the above dry process, a wet process such as compound precipitation or etching is also effective.

FIG. 14 is a diagram showing another method for forming irregularities on the surface. Fine particles 121 are arranged in a single layer or multiple layers on the substrate 120 to form irregularities. At this time, if the particle size of the particles 121 is too small, the effect of the unevenness on the size of the droplet is lost, and if it is too large, the reagent penetrates into the recesses and becomes wet. Therefore, theoretically, the particles 121 have a diameter of 5 nm to 100 μm. However, practically low-cost and easily available particles have a size of 10 to 500 nm. The particles were arranged by dipping the nozzle in a liquid in which the particles were dispersed in alcohol, but the particles may have a single particle size or a mixed particle size, and the arraying method may be one time or several times. Any of the arrangement may be used, and the particles may be arranged by a spray method or the like.

The surface irregularities described with reference to FIGS. 12, 13 and 14 are at least statistically self-similar and have a fractal dimension that can be defined. If the fractal dimension is approximately 2.2 or more. Effective in improving liquid drainage. However, when the fractal dimension is about 2.8 or more, the complexity increases, and the projections are easily disordered due to excessive clutter, so that the effect of unevenness cannot be obtained.

The surface tension of the fluororesin layer or the compound layer containing fluorine is preferably 30 mN / m or less in order to make the contact angle of the aqueous reagent 65 degrees or more. The surface tension was calculated by using Young's equation of solid-liquid interface balance, assuming that the interfacial tension of the solid-liquid is sufficiently smaller than the surface tension of the solid, and setting the surface tension of water to 72 mN / m. Further, when the contact angle is 65 degrees or more, the variation amount of the discharged reagent is 1
It has been confirmed that the content is within 0% and the liquid drainage property is good.

The film thickness of the fluororesin layer was in the range of 1 to 20 μm this time, although it depends on the dipping conditions. The film thickness of the compound layer containing fluorine was 5 to 100 nm. When a fluororesin or a compound containing fluorine is coated, the film thickness becomes thin at the edge portion of the nozzle, and holes penetrating to the thermally oxidized silicon are easily generated. In this case, the alkaline reagent dissolves the thermal silicon oxide, and the compound layer containing fluorine peels off. As shown in FIG. 10, the edge portion has a cross-sectional shape of arcs 111, 11
When SR processing is performed so as to be 2, the film thickness of the fluororesin layer or the compound layer containing fluorine becomes uniform, no through holes are generated, and the compound layer containing fluorine does not peel off even with an alkaline reagent. It is clear from the result of Example 3 of the result of the reagent discharge test shown in FIG.

[0047]

According to the present invention, a reagent is not wasted, a cleaning liquid is hardly required, and periodic disassembly and cleaning are not required, and it is easy to control a small amount of a reagent supply and a simple nozzle is provided. In addition, it is possible to provide a chemical analysis device having a nozzle that has a good liquid draining property of a reagent, a high ejection accuracy, and a high chemical resistance.

[Brief description of drawings]

FIG. 1 is a configuration diagram of a chemical analyzer according to the present invention.

FIG. 2 is a vertical cross-sectional view showing the configuration of a reagent supply unit that is an element of the chemical analysis device of the present invention.

FIG. 3 is a plan view of FIG.

FIG. 4 is a perspective view of a single nozzle of a micropump provided in the reagent supply mechanism according to the present invention.

FIG. 5 is a cross-sectional view of a nozzle included in the reagent supply mechanism according to the present invention.

FIG. 6 is a cross-sectional view of another nozzle according to the present invention.

FIG. 7 is a sectional view of still another nozzle according to the present invention.

FIG. 8 is a sectional view of still another nozzle according to the present invention.

FIG. 9 is a diagram showing the results of a reagent discharge test of the nozzles of the examples of the present invention and the nozzle of the comparative example.

FIG. 10 is a diagram showing a state in which a reagent is discharged from a discharge hole of a nozzle having a fluororesin layer on the surface according to the present invention.

FIG. 11 is a diagram showing a state in which a reagent is discharged from a discharge hole of a nozzle having a silicon dioxide layer on its surface.

FIG. 12 is a diagram illustrating an uneven shape formed on the surface of a nozzle substrate according to the present invention.

FIG. 13 is a diagram illustrating another uneven shape formed on the surface of the nozzle substrate according to the present invention.

FIG. 14 is a diagram illustrating a coating layer of silicon dioxide fine particles formed on the surface of a nozzle substrate according to the present invention.

[Explanation of symbols]

11 Device Main Body Upper Part 12 Device Main Body Front Part 21 Test Tube 22 Sample Holder 31 Sample Pipette 32 Nozzle 41 Reaction Container 43 Constant Temperature Bath 52 Reagent Container 53 Reagent Holder 54 Micro Pump 542 Discharge Hole 100, 100A, 100B, 100C, 100D Nozzle 101 ejection hole 102 nozzle substrate 103 silicon dioxide layer 104 fluororesin layer 107 Au layer

─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Takao Terayama 882 Ichige, Itamachi, Hitachinaka City, Ibaraki Prefecture Hitachi Ltd., Measuring Instruments Division (72) Inventor Takeshi Shibuya 882, Igemo, Hitachinaka City, Ibaraki Hitachi, Ltd. Mfg. Co., Ltd. (56) References JP-A-8-114601 (JP, A) JP-A-7-83935 (JP, A) JP-A-7-60972 (JP, A) JP-A-62-106371 ( JP, A) Special table 2000-500567 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) G01N 35/10

Claims (4)

(57) [Claims] 1. A reaction container holder for holding a plurality of reaction containers for containing a sample, a plurality of reagent containers for respectively containing various reagents to be added to a sample in the reaction container, and a plurality of reagent containers attached to the lower part of the reagent container. In a chemical analyzer equipped with a pump for inhaling a fixed amount of reagent and instilling it into the reaction container, and a measuring device for measuring the physical properties of the sample after the reagent is added, the pump is a silicon pump body. A nozzle made of silicon, which is joined to the front surface of the pump body and has a discharge hole at the center of the plate that is connected to the outlet of the pump body. A chemical resistant layer having corrosion resistance to the reagent is formed on the inner surface, and a fluororesin layer is further formed on the chemical resistant layer on the front surface of the substrate or on the front surface of the plate and the inner surface of the discharge hole. Alternatively, a chemical analyzer characterized in that a compound containing fluorine is formed. 2. The chemical resistant layer comprises silicon dioxide, A
The chemical analyzer according to claim 1, which is made of u, Ag, Pt or a corrosion resistant alloy. 3. The surface of the fluororesin layer is made uneven.
Alternatively, the chemical analyzer according to item 2. 4. The chemical analysis device according to claim 2, wherein the discharge hole in the substrate has a rounded chamfered edge.