JP2000146989A - Chemical analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a nozzle and a pump which do not require a cleaning operation, by which a reagent in a trace amount is controlled easily and whose chemical resistance is high, by a method wherein a chemical-resistant layer is formed on the surface and the rear of a silicon nozzle substrate having a discharge hole and on the inner surface of the discharge hole and a fluororesin layer or a fluorine compound layer is formed on the front of the substrate or the front of a plate and on the inner surface of the discharge hole. SOLUTION: A nozzle substrate 102, a silicon dioxide layer 103 which is formed on the substrate 102, an Au layer 107 which is formed on it and a fluoresin layer 104 which is formed on the rear surface of the substrate 102 and on the Au layer 107 at the inside of a discharge hole 101 constitute a nozzle 100. The layer 103 is formed by a thermal oxidation operation, its film thickness can be controlled at several nm to 1 μm, and the chemical resistance of the substrate 102 is enhanced, The Au layer 107 is formed by a sputtering operation or a plating operation, its film thickness can be controlled at several nm or higher, and the chemical resistance of the substrate 102 is enhanced. When the layer 107 is formed, the alkali resistance and the acid resistance of a nozzle and a pump are increased, and the exfoliation of the layer 104 is prevented.

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 determining the concentration of a substance dissolved in a liquid, and more particularly to a chemical analyzer for analyzing components such as biological fluids and water.

[0002]

2. Description of the Related Art A conventional chemical analyzer in a general form is the chemical analyzer described in US Pat. No. 4,451,433. This device consists of a colorimetric measurement unit for analyzing and quantifying proteins, enzymes, components in urine, etc. in blood, and an ion analysis unit for analyzing ions in blood. From 9
It has a processing speed of over 000 tests.

There are dozens of colorimetric measurement items of a chemical analyzer represented by the above-mentioned prior art, and at least about ten types of items are analyzed for a single specimen even in a normal inspection item. In order to perform these items with one apparatus, a mechanism is provided for selecting a reagent from a plurality of reagent containers and sequentially supplying the reagent to the reaction container in a predetermined amount of the reagent. In the case of the above prior art, a method called a reagent pipetting mechanism is employed as a supply mechanism.

The reagent pipetting mechanism mainly comprises a nozzle for sucking and holding a reagent therein, a mechanism for moving the nozzle three-dimensionally, and a suction / discharge control pump for sucking and discharging a sample into the nozzle. In order to transmit the suction / discharge operation of the pump to the nozzle with good responsiveness, the pipeline 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 two are separated by air. This air layer is formed by sucking air into the nozzle before sucking the reagent. The supply of the reagent is performed in the following manner.

First, a nozzle is immersed in a reagent container by a three-dimensional moving mechanism, and a predetermined amount of reagent is sucked into the nozzle. Thereafter, the reagent leaves the reagent container and moves to the upper portion of the reaction container, and discharges the reagent inside the nozzle. After discharging the reagent, the inside and outside of the nozzle are flushed with a cleaning liquid in the nozzle cleaning tank in order to avoid contamination of the next reagent. Since the trajectory where the nozzle of the reagent pipetting mechanism moves is determined, a reagent container moving mechanism for positioning the reagent container is provided below the moving path. This reagent supply mechanism requires a relatively long time for nozzle three-dimensional movement and cleaning, so the number of tests per unit time is limited. However, this system is suitable for analyzing a relatively large number of items. It is.

As another reagent supply mechanism, there is a dispenser mechanism including a syringe pump, a flow path switching valve, and a reagent discharge nozzle. Tubes are collected from the reagent containers in the flow path switching valve. The same number of tubes extend from each valve to each reagent discharge nozzle. Furthermore, one 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 to connect the tube extending from the corresponding reagent container to the syringe pump. The syringe pump performs a suction operation, and draws a predetermined amount of reagent into the tube on the syringe pump side via the switching valve.

Next, the switching valve is operated to connect a tube from the syringe pump to the switching valve and a tube connected from the switching valve to the reagent discharge nozzle. In this state, the syringe pump performs a discharging operation to discharge a predetermined amount of the reagent in the tube into the reaction container. In this system, the switching and supply of the reagent can be performed at a high speed. Further, the reagent discharge nozzle has only the type of the reagent, and there is no need to clean the inside of the tube following the nozzle. However, since a reagent ejection nozzle needs to be provided for each type of reagent, it is not suitable when there are many types of reagents to be used. Rather, it is suitable for analyzing items with few types but many tests.

[0008] Still another prior art is disclosed in Japanese Patent Application Laid-Open No. 63-13 / 1988.
There is an automatic analyzer of Japanese Patent No. 1066. The first object of the present invention is to reduce the size of the apparatus by making the movement locus of the reagent container holder holding the reagent container overlap the movement locus of the reaction container holder holding the reaction container. The reagent is discharged by a piston integrally formed on the side surface of each reagent container. The drive of the piston is
This is performed by a piston rod driving device provided at the reagent discharge position. At the discharge position, the piston rod drive of the reagent container is temporarily connected.

Next, the piston rod is pulled up to suck the reagent in the reagent container into the piston. When it reaches the top, it engages with the gear that rotates the piston,
The gear rotates the piston 180 degrees. At this time, the hole opened for suction is closed by the rotation of the piston, and the hole connected to the discharge port is opened. As the piston rod moves downward, the reagent in the piston is discharged into the reaction vessel through the hole.

On the other hand, Japanese Patent Application Laid-Open No. 7-60972 discloses that the nozzle of an ink jet head is formed integrally with a flow path substrate made of acrylonitrile butadiene styrene (ABS) resin, the nozzle surface is made highly water repellent, and the flow path inside the nozzle is formed. A method of manufacturing an inexpensive inkjet head in which the ink jetting force is increased and the number of components is reduced by making the ink jetting hydrophilic.

[0011]

The above-described prior art reagent supply mechanism has the following problems.

In the case of the reagent pipetting mechanism, there are the following three problems. The first is that an unnecessary amount of reagent is generated. That is, an air layer is provided between the nozzles to prevent the reagent sucked into the nozzle from mixing with the pure water. However, the pure water mixes with the upper part of the reagent along the inner wall of the nozzle. Therefore, in order to prevent the mixed reagent from being used for analysis, the reagent is sucked into the nozzle about 30% more than the amount of reagent actually required for analysis. The reagents used in the present analysis are very expensive, and thus the extra amount of reagents leads to waste of test costs.

Second, a large amount of time and liquid is required for cleaning. That is, in order to avoid mixing of the reagents via 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 extra washing time for that purpose are required. Further, the third problem is that even if the inside and outside of the nozzle are washed with the cleaning liquid, some residue is generated, which causes an error in the measured value.

The reagent dispenser mechanism has the following two problems. The first is that a wasteful amount of reagent is generated as described above. In order to quickly discharge reagents for all reagents, all reagents must be filled in tubes from the reagent container to the switching valve and tubes from the switching valve to the discharge nozzle before starting analysis. There is. The reagent filled in this portion is wasted when the apparatus is stopped. Depending on the type of reagent and the total length of the tube, more than a hundred reagents may be wasted. The second problem is that
The maintenance of the switching valve is a troublesome point. That is, different reagents pass through the switching valve one after another, so that the switching valve gradually becomes dirty. When different reagents touch each other, the valve seat may stick. Therefore, it is necessary to periodically disassemble and clean the switching valve.

Further, in the piston system of the third example,
Although the amount of waste reagent is small compared to any of the above examples,
Nevertheless, when the apparatus is shut down, there is a flow path from the reagent container to the tip of the pipetter, so that the reagent remains and this part is wasted. The amount of reagent to be supplied must be changed according to the concentration of the sample, but the amount of reciprocating movement of the piston is determined in advance because the position of the gear provided for rotation on the upper part of the piston is fixed. Only the amount of reagent that has been discharged can be discharged. Further, since the piston is provided on the side surface, it is necessary to temporarily pump the reagent to a position higher than the position of the reagent container. Further, 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, and the driving mechanism of the piston becomes complicated and large. That is, the use of a simple and small pump is hindered.

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

In order to solve the above-mentioned problems, it is necessary to improve the reagent dropping method, the pump structure, the structure of the analyzer, and the like. It is necessary to improve controllability. For that purpose, it is important to improve the structure of the nozzle and the function of draining the liquid. Acrylonitrile butadiene styrene (AB) described in JP-A-7-60972 concerning improvement of nozzle function
S) Substrates and water-repellent coatings have low chemical resistance and are good for inks as fluids, but have problems in using them for chemical analysis such as discharging acidic or basic reagents.

Therefore, an object of the present invention is to make the control of the amount of the supplied reagent easy, without wasting the reagent, hardly requiring a cleaning solution, and not requiring periodic disassembly and cleaning.
An object of the present invention is to provide a chemical analyzer having a simple nozzle, high discharge resolution and discharge stability, and a chemical resistant nozzle and a pump, and to propose a manufacturing method thereof.

[0019]

Means for Solving the Problems To achieve the above object, a chemical analyzer of the present invention comprises a reaction container holder for holding a plurality of reaction containers for holding a sample, and various kinds of components to be added to the sample in the reaction container. A plurality of reagent containers for storing the reagents one by one, a pump attached to the lower portion of the reagent container for absorbing a predetermined amount of the reagent and injecting it into the reaction container, and a measurement for measuring the physical properties of the sample after the reagent is added The pump comprises a silicon pump body, a silicon nozzle joined to the front surface of the pump body, and having a plate-like shape and having a discharge hole connected to an outlet of the pump body at the center of the plate. A chemical-resistant layer having corrosion resistance to the reagent is formed on the front and back surfaces of the substrate of the nozzle and the inner surface of the discharge holes, and the front surface of the substrate or the front surface of the plate and the discharge holes are formed. The surface, the fluorine resin layer on the chemical layer,
Alternatively, a compound containing fluorine (eg, a fluorocarbon compound CF ₃ (CF ₂ ) _m (CH ₂ ) nSi (OCH ₃ ) ₃ ) is formed.

Further, in the above-described method for manufacturing a chemical analyzer, a chemical-resistant layer having corrosion resistance to the reagent is formed on the front and back surfaces of the substrate of the nozzle and the inner surface of the discharge hole by sputtering. Alternatively, a fluorine resin or a compound containing fluorine is spray-coated or immersed on the chemical-resistant layer on the front surface of the plate and the inner surface of the discharge hole, and then heated and dried.

After forming a plurality of pores in the direction of the inner surface of the nozzle by silicon micromachining or hydrofluoric acid electrolytic etching on the front and back surfaces of the substrate of the nozzle and the inner surface of the discharge hole, a chemical resistant layer is formed. It is preferable to form a layer containing a fluorine resin or a compound containing fluorine, whereby the chemical resistance of the fluorine resin or the compound layer containing fluorine is further improved.

After the chemical resistant layer is formed, it is preferable to irradiate the surface of the chemical resistant layer with ions or atoms of oxygen, water vapor, hydrogen, or ozone by a dry process. When activated, the bond with the fluorine resin or the fluorine-containing compound layer becomes strong, and the chemical resistance is further improved.

When the material of the discharge pump and the nozzle is made of silicon, fine processing can be performed by using a semiconductor manufacturing process, and mounting on a reagent bottle is possible. Furthermore, if a compound of silicon is formed on the surface of silicon,
Chemical resistance is further improved.

[0024]

DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of a chemical analyzer according to the present invention will be described with reference to FIGS. FIG.
FIG. 2 is an overall configuration diagram of a chemical analyzer having a reagent supply mechanism of the present invention, FIG. 2 is a detailed explanatory view of the reagent supply mechanism, FIG. 3 is a plan view of FIG. 2, and FIG. FIG. 5 is an exploded perspective view of the provided pump nozzle, and FIG. 5 is a sectional view of the pump nozzle. FIG. 6 is an enlarged sectional view of a part of the surface of the nozzle according to the present invention, and FIG. 7 is an enlarged sectional view of a part of the surface of another nozzle according to the present invention. FIG. 8 is an enlarged perspective view of a part of the surface of the nozzle according to the present invention, and FIG. 9 is an enlarged perspective view of a part of the surface of another nozzle according to the present invention. FIG. 10 is an enlarged side view of a part of the surface of another nozzle according to the present invention. FIG. 11 shows the results of testing the durability of the nozzle of the present invention and the nozzle of the comparative example. FIG.
FIG. 13 is a cross-sectional view of a nozzle showing a state of a reagent after a reagent is discharged from a reagent discharge hole of a nozzle in a practical form according to the present invention. FIG. FIG.

First, the structure of the chemical analyzer of the present invention will be described with reference to FIGS. FIG. 1A is a plan view of the chemical analyzer 11, and FIG. 1B is a front view thereof. At the top of the chemical analyzer 11, a sample holder 22 for holding the test tubes 21 containing the samples 20 arranged in a circular shape in a plane is provided. A sample pipetter 31 for sucking the sample 22 in the test tube 21 is provided beside the circle in which the sample holders 22 are arranged. The sample pipetter 31 sucks a sample from the test tube 21 and holds it inside, a three-dimensional drive mechanism 33 that moves the nozzle 32 up and down, and turns, and sucks and discharges the sample into the nozzle 32. A pump (not shown) is provided.

The sample holder 22 includes a plurality of test tubes 2.
The rotary drive mechanism 23 is driven to rotate the sample pipets 1 immediately below the nozzles 32 of the sample pipettor 31 one by one. Next to the sample holder 22,
A reaction disk 42 is provided as if sandwiching the sample pipettor 31.

The reaction disk 42 includes a plurality of reaction vessels 41.
Are arranged in a circular shape in a plane, and are sequentially rotated to move the reaction vessel 41 to the other lower position of the nozzle 32 of the sample pipettor 31. The lower half of each reaction vessel 41 is immersed in a constant temperature bath 43 through which constant temperature water flows. In order to sequentially move the reaction vessel 41 to the lower position of the nozzle 32 of the sample pipettor 31, the reaction disk 4
2 is supported by a reaction disk rotation drive mechanism 44.
Above the outer peripheral edge of the reaction disk 42, a reaction vessel cleaning mechanism 71 and a spectrometer 81 are provided in this order.

The configuration of the reagent supply section 51 will be described in detail with reference to FIGS. The reagent supply unit 51 includes:
It is roughly composed of four parts: a plurality of reagent containers 52, a reagent holder 53 for holding the reagent containers 52, a micropump 54, and a reagent holder rotation drive mechanism 55. The reagent holder 53 holds the reagent container 5 around the central axis 56.
2 is held on the circumference. As many membrane pumps 54 as the number of reagent containers 52 to be held are provided at the bottom of the reagent holder 53. A connection hole 521 is provided on the bottom surface of the reagent container 52. The connection hole 521 is connected to the suction hole 541 of the micro pump 54 by strongly pressing the bottom of the reagent holder 53.

A nozzle 100 is joined to the tip of the micropump 54, and a discharge hole 542 formed in the nozzle 100 is provided vertically downward. Here, the nozzle 100 is a generic name of several nozzles described later. On the side surface of the reagent container 52, a magnetic section 522 in which data describing the type of the reagent is written is provided. At a corresponding circumferential position of the reagent holder 53, a magnetic reader 531 for reading data of the magnetic section 522 is provided.

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 a micro pump control unit 58. Reagent holder 5
Reference numeral 3 is configured to be rotationally moved by a reagent holder rotation drive mechanism 55. Note that the second reagent supply unit 61 is configured similarly to the first reagent supply unit 51.

FIG. 4 shows the first and second reagent supply units 51 and 6.
FIG. 3 is an external view of a nozzle 100 attached to one micro pump 54 and a discharge hole 542. 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), and the upper part 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 other shapes.

An embodiment of the nozzle attached to the tip of the micropump will be described below.

(Embodiment 1) FIG. 5 shows the nozzle 1 of Embodiment 1.
FIG. 5 is a cross-sectional view (AA cross section in FIG. 4) illustrating the configuration of No. 00. The nozzle 100 includes a nozzle substrate 102 having a plate shape made of silicon and having discharge holes formed at the center of the plate, and a nozzle substrate 102.
Silicon dioxide layer 103 forming a surface of silicon dioxide, and Au layer 107 further formed on silicon dioxide layer 103
And a fluororesin layer 104 formed on the Au layer 107 on the lower surface of the nozzle substrate 102 and the inner surface of the ejection hole 101.
And is composed of

FIG. 6 is an enlarged sectional view of a part of the surface of the nozzle 100 of the first embodiment. In the nozzle substrate 102, pores 114 are formed in the direction from the surface to the inner surface, and a silicon dioxide layer 103 formed on the nozzle substrate 102,
The Au layer 107 formed thereon is formed along the pores 114, and the fluororesin layer 107 is formed so as to fill the pores 114 and make the surface flat.

The material of the nozzle substrate 102, ie, silicon, can be processed into a minute and complicated shape by micromachining processing represented by a semiconductor process. The silicon dioxide layer 103 is formed by thermal oxidation, and its thickness can be controlled in a range from several nanometers to about 1 micron, and the chemical resistance of the nozzle substrate 102 is improved. The Au layer 107 is formed by sputtering or plating, and its thickness can be controlled to several nanometers or more.
2 improve the chemical resistance.

By providing the Au layer 107, even if a pinhole is present in the fluororesin layer and the reagent is permeated, Au has high alkali resistance and acid resistance and does not elute, so that the fluororesin layer 104 is difficult to peel off. . Furthermore, A
If the u layer 107 is formed on the surface opposite to the reagent ejection side, this surface is a surface that is bonded to the main body of the micropump 54, and the presence of Au improves the bonding property. The Au layer 107 is not limited to Au, but may be any as long as it has high chemical resistance. For example, a superalloy such as Hastelloy, a resin such as polypropylene, or Si ₃ ↓
Ceramics such as N ₄ ↓, Ag and Pt may be used. Further, it is desirable to use a metal in order to improve the bondability with the liquid sending means. The silicon dioxide layer 10
3. The thickness of the Au layer 107 is set so as not to fill the pores 114.

The pores 114 are formed by hydrofluoric acid electrolytic etching. The maximum diameter of the pores 114 is several nanometers to several tens of micrometers, and the depth of the pores 114 is several hundred micrometers depending on hydrofluoric acid electrolytic etching conditions. It can reach the meter. The fluororesin layer 107 is formed by baking at a temperature of 100 ° C. to 250 ° C. after dipping or spray coating, and has a thickness of about 10 nm or more. However, the thickness of the fluororesin layer 107 is preferably about 100 nm or more in order to fill and form the pores 114. When the fluororesin layer 107 fills the pores 114, an anchor effect is generated, and the adhesion strength is mechanically improved. The fluororesin layer 104 is formed on the lower surface of the nozzle substrate 102 and the discharge holes 101.
Gives water repellency to the inner surface.

The hydrofluoric acid electrolytic etching was performed by heating the silicon nozzle substrate 102 to 40 ° C. using the anode as an anode.
The test was performed by immersing in a 0% hydrofluoric acid aqueous solution and applying a current of 10 mA / cm ² for 15 minutes.

Example 2 In the same manner as in Example 1, a thermal silicon oxide layer was formed on a silicon nozzle substrate, and then a fluorine-containing compound layer was formed. The compound containing fluorine is a compound containing a fluoroalkylsilane.

(Embodiment 3) FIG. 7 shows the nozzle 1 of Embodiment 3.
FIG. 10 is a cross-sectional view of a part of the surface of the nozzle showing another configuration of 00. 6 is different from the nozzle 100 shown in FIG. 6 in that the fine holes 115 formed on the surface of the nozzle substrate 102 are continuously connected to the fine holes 115 formed in the vicinity to form irregularities. Silicon dioxide layer 103, Au layer 107
Does not fill the pores 115 and furthermore
The structure for filling the pores is the same as in the first embodiment. Pore 1
15 is an aqueous solution of 50% hydrofluoric acid heated to 50 ° C.
It was formed by immersion for 0 minutes. The anchor effect of the fluororesin layer 104 is the same as in the first embodiment. The pores can be formed by wet etching with a mixed acid composed of hydrofluoric acid, hydrochloric acid, nitric acid, sulfuric acid, or the like, or by dry etching with irradiation of atoms or ions.

Example 4 Instead of the fluororesin of Example 3, a compound layer containing fluorine was immersed in
It was formed by baking for 0 minutes. The compound containing fluorine is a compound containing a fluoroalkylsilane.

(Embodiment 5) FIG. 8 shows that a convex 110 and a concave 111 are formed on the surface of a silicon nozzle substrate 102 by a micromachining process. Thereafter, a thermally oxidized silicon layer 103, an Au layer 107, and a fluororesin layer 104 were formed as in Example 1. The recess 111 has the same anchor effect as the pores 114 and 115 shown in the first to fourth embodiments.
The adhesiveness of the fluororesin layer 104 is improved, and the chemical resistance is improved.

Example 6 A fluorine-containing compound layer was formed instead of the fluororesin layer of Example 5.

(Embodiment 7) In FIG. 9, a convex 112 and a concave 113 are formed on the surface of a silicon nozzle substrate 102 by a micro-machine process. Thereafter, a thermally oxidized silicon layer 103, an Au layer 107, and a fluororesin layer 104 were formed as in Example 1. In this case, the convex portion 112 has an anchor effect, increases the adhesion of the fluororesin layer 104, and improves the chemical resistance.

(Embodiment 8) FIG. 10 shows that the surface of a silicon nozzle substrate 102 is immersed in a sol solution composed of ethanol and ethyl silicate in which fine particles of silicon dioxide having a particle diameter of 120 nm are dispersed, and a speed of 3 mm / min. , And dried at 150 ° C. for 30 minutes for coating. Thereafter, the same fluororesin layer 104 as in Example 1 was formed. The particle size of silicon dioxide is not limited to
The anchor effect of the fluororesin layer 104 is exhibited at about 0 nm to about 50 μm. In addition, the silicon dioxide layer exhibits an anchor effect both in a single layer and in multiple layers, but a multilayer coat is more effective.

(Embodiment 9) The nozzle 10 shown in Embodiment 1
In the 0A manufacturing process, a step of irradiating oxygen plasma was performed before forming the fluororesin layer 104.

(Embodiment 10) Nozzle 1 shown in Embodiment 1
In the manufacturing process of 00A, a step of irradiating steam plasma was performed before forming the fluororesin layer 104.

(Embodiment 11) Nozzle 1 shown in Embodiment 1
In the manufacturing process of No. 00, before forming the fluororesin layer 104, a step of irradiating the nozzle 100 with oxygen using a plasma generator was performed.

(Example 12) Nozzle 1 shown in Example 1
In the manufacturing process of No. 00, a step of irradiating ozone with a plasma generator was performed before forming the fluororesin layer 104.

(Embodiment 13) Nozzle 1 shown in Embodiment 1
In the manufacturing process of No. 00, a process of irradiating oxygen using a plasma generator was performed without performing the hydrofluoric acid electrolytic etching process for forming pores and before forming the fluororesin layer 104.

(Embodiment 14) Nozzle 1 shown in Embodiment 1
In the manufacturing process of No. 00, a process of irradiating water vapor using a plasma generator was performed without performing the hydrofluoric acid electrolytic etching process of forming pores and before forming the fluororesin layer 104.

(Embodiment 15) Nozzle 1 shown in Embodiment 1
In the manufacturing process of No. 00, a process of irradiating hydrogen with a plasma generator was performed without performing the hydrofluoric acid electrolytic etching process for forming pores and before forming the fluororesin layer 104.

(Example 16) Nozzle 1 shown in Example 1
In the manufacturing process of 00A, a process of irradiating ozone using a plasma generator was performed without performing a hydrofluoric acid electrolytic etching process for forming pores and before forming the fluororesin layer 104.

The process using the plasma generators of Examples 9 to 16 was performed at 2 × 10 ^-3 equipped with a plasma generator.
This is a process in which oxygen, water vapor, hydrogen, or ozone is introduced into a Torr vacuum device and the treatment is performed for 60 minutes.

Comparative Example 1 A silicon dioxide layer was provided on the surface of a nozzle of a silicon substrate by thermal oxidation.

Comparative Example 2 A silicon dioxide layer was provided on the surface of a nozzle of a silicon substrate by thermal oxidation. Thereafter, a fluororesin layer was formed by dipping.

Comparative Example 3 A silicon dioxide layer was provided on the surface of a nozzle of a silicon substrate by thermal oxidation. Thereafter, an Au layer was formed by sputtering, and a fluorine resin layer was formed thereon by dipping.

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

The Au layer was formed by sputtering, and the reagent ejection side surface of the nozzle and the opposite surface were sequentially coated.
If there is an apparatus capable of simultaneously sputtering two surfaces, it is possible to shorten the sputtering time.

Although silicon was used for the nozzle material because of the ease of performing the micromachine process, the material is not particularly limited to silicon, and may be glass, ceramics such as alumina or zirconia, or metal materials such as SUS. A resin such as PTFE may be used. The nozzle 102
The micromachining process was used for the processing of the projections 110 and 112 and the recesses 111 and 113, which are excellent in processing of a fine structure, processing accuracy when mass processing is performed, and mass productivity. Used for. However, the present invention is not limited to the micromachine process, but may be machining or injection molding using a resin material.

Although the fluororesin layer 104 is formed on the inner wall surface of the discharge hole 101 of the nozzle, it is indispensable on the lower surface of the nozzle substrate, and need not be formed on the inner wall surface of the discharge hole. . This is a difference from the viewpoint of the water repellency of the fluororesin layer whether the position of the interface between the liquid and the air when the liquid runs out becomes the nozzle tip surface or the hole of the nozzle discharge hole.

The nozzles of Examples 1 to 16 and Comparative Examples 1 to 3 were subjected to a reagent immersion test and a discharge test to examine the durability of the fluororesin layer or the fluorine-containing compound layer. The immersion test method was a method in which a nozzle was immersed in a reagent at room temperature, taken out at an arbitrary time, observed under a microscope, and the presence or absence of peeling of a compound layer including a fluororesin layer or a fluorine layer was confirmed. The ejection test method is to repeatedly eject the reagent 1000 times, observe the nozzle as in the immersion test,
The presence or absence of peeling of the fluorine resin layer or the compound layer including the fluorine layer was confirmed.

FIG. 11 shows the test results. In the case of the immersion test, the case where the fluororesin layer or the compound layer containing fluorine was not peeled after immersion for 40 days or more was regarded as acceptable, and the adhesion less than 40 days was regarded as poor adhesion. According to this, from the results shown in FIG. 11, Examples 1 to 16 passed, and the comparative example failed. As a result of the discharge test, Examples 1 to 16
It did not peel off even after the 100th discharge, and the adhesion of the fluorine resin layer or fluorine compound layer was good. In Comparative Examples 1 to 3, peeling occurred.

Here, the effect of improving the discharge performance by forming a fluorine resin layer or a fluorine-containing compound layer on the nozzle will be described with reference to FIGS. 12 and 13. FIG.

FIG. 12 is a view showing a state where the reagent is discharged from the nozzle 102 and the reagent is about to be interrupted. Since the surface tension of the fluororesin layer or the fluorine-containing compound layer 104 is low, the reagent becomes a liquid droplet 116. When the size of the liquid droplet 116 becomes a certain size, the reagent becomes the liquid droplet 116 or the fluorine-containing compound layer 104. Affected by surface tension,
Separate from the reagent filling the nozzle hole. Therefore, the reagent is easily interrupted, and the stability of the amount of the discharged reagent is also improved.

On the other hand, FIG. 13 is a view showing the state of the reagent after the reagent is discharged from the nozzle on which the fluorine resin layer or the compound layer containing fluorine is not formed. The reagent 117 is
When the reagent is spread on the reagent discharge side of the nozzle and then the reagent is discharged next, the wet and spread reagent is also discharged, and the stability of the amount of the reagent is not good. Also, the sharpness of the reagent is low.

It is necessary that the fluororesin layer or the compound layer containing fluorine is hardly wetted by the reagent. The reagent to which the alcohol-based reagent or the surfactant was added had a lower surface tension than the aqueous-based reagent, so that the contact angle was low.

When the nozzle substrate is made of a material other than silicon, micromachining can be easily used by coating the substrate with silicon. In the case of resin,
Irregularities can be formed on the surface by a dry process such as ion implantation or plasma irradiation. In the case of metal, a wet process such as compound deposition or etching is also effective in addition to the above dry process.

The surface tension of the fluororesin layer or the compound layer containing fluorine is desirably 30 mN / m or less in the case of an aqueous reagent in order to make the contact angle 65 degrees or more. The surface tension was calculated using the Young's solid-liquid interface equilibrium equation, assuming that the solid-liquid interface tension is sufficiently smaller than the solid surface tension, and the surface tension of water as 72 mN / m.

[0070]

According to the present invention, a small amount of reagent can be easily controlled and a simple nozzle is provided without wasting reagents, hardly requiring a cleaning solution, and not requiring periodic disassembly and cleaning. Further, it is possible to provide a chemical analyzer having a high discharge resolution and a high discharge stability and having a chemical resistant nozzle and a pump, and to propose a manufacturing method thereof.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a chemical analysis device of the present invention.

FIG. 2 is a longitudinal sectional view showing a configuration of a reagent supply unit which is an element of the chemical analyzer of the present invention.

FIG. 3 is a plan view of FIG. 2;

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 sectional view of a nozzle provided in the reagent supply mechanism according to the present invention.

FIG. 6 is a partially enlarged sectional view showing the configuration of the surface of the nozzle according to the present invention.

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

FIG. 8 is a partially enlarged perspective view showing a concavo-convex shape on the surface of still another nozzle according to the present invention.

FIG. 9 is a partially enlarged perspective view showing a concavo-convex shape on the surface of still another nozzle according to the present invention.

FIG. 10 is a view for explaining a coating layer of silicon dioxide fine particles formed on the surface of the nozzle substrate according to the present invention.

FIG. 11 is a diagram showing the results of reagent immersion and discharge tests of the nozzle of each example of the present invention and the nozzle of the comparative example.

FIG. 12 is a view 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. 13 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 the surface.

[Explanation of symbols]

11: Upper part of the apparatus main body, 12: Front part of the apparatus main body, 21 ...
Test tube, 22: sample holder, 31: sample pipettor, 32: nozzle, 41: reaction vessel, 43: constant temperature bath,
52: Reagent container, 53: Reagent holder, 54: Micropump, 100: Nozzle, 101: Discharge hole, 102: Nozzle substrate, 103: Silicon dioxide layer, 104: Fluororesin layer, 107: Au layer, 542: Discharge hole .

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Akira Koide 502, Kandachicho, Tsuchiura-shi, Ibaraki Pref. Machinery Research Laboratories, Hitachi, Ltd. 2G058 CB04 CD04 CE08 EA11 EB00 ED03 ED10 ED12 ED19 ED20 ED23 4F042 AA11 AA27 AB00 CB02 DB01 DH09

Claims (1)

[Claims] 1. A reaction container holder for holding a plurality of reaction containers for holding a sample, a plurality of reagent containers for respectively holding various reagents to be added to a sample in the reaction container,
In a chemical analyzer equipped with a pump attached to the lower part of the reagent container and absorbing a predetermined amount of reagent and instilling it into the reaction container, and a measuring device for measuring physical properties of the sample after the reagent is added, The pump is composed of a silicon pump body and a silicon nozzle joined to the front surface of the pump body and having a plate-like shape and having a discharge hole connected to an outlet of the pump body at the center of the plate. A chemical-resistant layer having corrosion resistance to the reagent is formed on the front and back surfaces of the substrate of the nozzle and on the inner surface of the discharge hole, and a plurality of pores are formed in the inner surface direction from the surface of the chemical-resistant layer. A chemical analyzer, wherein a fluorine resin or a compound containing fluorine is formed on the chemical resistant layer on the front surface or the front surface of the plate and the inner surface of the discharge hole.