JP2008309728A - Electrode for producing reaction cell for autoanalyzer, and production method using the electrode - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a reaction cell with excellent reliability, capable of preventing mutual contamination of a sample and a reagent between adjacent reaction cells with minimized adhesion of bubbles; a method for producing the reaction cell; and an autoanalyzer provided with the reaction cell. <P>SOLUTION: The invention provides a method and an electrode for uniformly and stably producing a transparent resin-made reaction cell for autoanalyzer such as biochemical autoanalyzer having an inner wall surface composed of a hydrophilic part and a hydrophobic part by corona discharge. A uniform and stable treatment is attained by use of corona discharge by appropriate electrode layout and appropriate electrode or air suction in corona discharge. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention includes a partial modification method for the inner wall surface of a reaction cell for spectrophotometric analysis used in an automatic analyzer for medical diagnosis such as biochemical analysis reaction and immune reaction, a modification electrode, and the reaction cell. Related to the automated analyzer.

  In clinical tests for medical diagnosis, biochemical analysis and immunological analysis of proteins, sugars, lipids, enzymes, hormones, inorganic ions, disease markers, etc. in biological samples such as blood and urine are performed. In clinical examination, since it is necessary to process a plurality of examination items with high reliability and at high speed, most of the examination items are executed by an automatic analyzer. Conventionally, as an automatic analyzer, for example, a biochemical analyzer that performs biochemical analysis by measuring the absorbance of a reaction solution obtained by mixing a desired reagent with a sample such as serum and reacting it is known. It has been. This type of biochemical analyzer includes a container for storing a sample and a reagent, a reaction cell for injecting the sample and the reagent, a mechanism for automatically injecting the sample and the reagent into the reaction cell, and mixing the sample and the reagent in the reaction cell. Automatic stirring mechanism, a mechanism for measuring the spectral spectrum of the sample during or after the reaction, an automatic cleaning mechanism for aspirating and discharging the reaction solution after the spectral spectrum measurement is completed, and washing the reaction cell, etc. (For example, Patent Document 1).

  In the field of automatic analyzers, miniaturization of samples and reagents has become a major technical issue. In other words, with the increase in the number of analysis items, the amount of sample that can be divided into single items has decreased, and the sample itself may be valuable and cannot be prepared in large quantities. It has come to be done routinely. In addition, as the analysis content becomes more sophisticated, reagents are generally more expensive, and there is a demand for reducing the amount of reagents in terms of cost. Such a small amount of sample and reagent is also a strong motivation for further miniaturization of the reaction cell. In addition, miniaturization of the reaction cell and a reduction in the amount of necessary samples and reagents have advantages that lead to improvement in analysis throughput and low waste liquid.

  Here, a reaction cell (also called a reaction vessel) used for a general automatic analyzer is generally formed of glass or synthetic resin. For example, according to Patent Document 2, the material of the reaction cell is selected from resin materials having low water absorption, low moisture permeability, high total light transmittance, low refractive index, and low molding shrinkage. Specifically, one type selected from polycycloolefin, polycarbonate resin, acrylic resin, and polystyrene resin is preferably exemplified. In addition, Patent Document 2 discloses a problem related to a synthetic resin reaction cell, which is to reduce initial detection failure in which bubbles generated when a biological sample and a reagent flow into the cell adhere to the inner wall of the cell and cannot be measured. Cite. At this time, the cause of bubble adhesion is that the wettability of the cell inner wall surface is low.

  Effective synthetic resin (also called plastic or polymer resin) surface wettability, that is, effective means for hydrophilizing the surface include oxygen plasma treatment, ozone treatment, ozone water treatment, corona discharge treatment, and UV treatment. Etc. are known. According to Non-Patent Document 1, surface modification by forming a graft polymer after introducing peroxide on the surface by oxidizing the polyethylene surface, which is a kind of polymer resin, by corona discharge treatment. Is possible. Patent Document 3 reports oxidation and hydrophilization of a plastic container by ozone treatment.

Japanese Patent No. 1706358 JP 2005-30763 A JP 2000-346765 A Journal of Polymer Science: Part A: Polymer Chemistry, Vol.26, 3309-3322.

  In the field of automatic analyzers, the amount of samples and reagents is becoming increasingly smaller, and the demand for miniaturization of the apparatus is increasing. For this reason, the following two problems have emerged as new problems that have not been regarded as problems. The size of the reaction cell used in the past was sufficiently large compared to bubbles, so even if the bubbles hit the optical axis, the absorbance hardly fluctuated within the practical range, and it was extremely rare to have trouble. It has been found out that the influence of bubbles becomes obvious in experiments for reducing the reaction cell volume. The cause of this problem is the hydrophobicity of the transparent resin used for the reaction cell material. Therefore, when the inner wall surface of the reaction cell was made hydrophilic, it was confirmed that no bubbles adhered.

  However, when the hydrophilic treatment on the inner wall surface of the reaction cell was performed entirely, the second problem emerged. When the inner wall of the reaction cell is hydrophilized from the bottom to the top opening, the test solution rises to the edge of the reaction cell by capillary action, and cross-contamination that mixes with the reagent of the adjacent reaction cell easily occurs.

  In addition, although the phenomenon is similar to the above, reaction cells that have been used once are used in sequence after cleaning, but the components of the reaction solution remaining on the inner surface of the reaction cell are mixed in the next analysis, which adversely affects measurement data. There is a case. This phenomenon is called cross contamination. Some of the reaction liquid components that may remain on the inner surface of the reaction cell include hydrophilic substances such as proteins and inorganic ions in addition to lipids.

Miniaturization of reaction cells tends to promote cross-contamination and is expected to become a bigger problem in the future. In order to cope with the constant trend of miniaturization of automatic analyzers and a small amount of samples and reagents, it is necessary to solve the above two problems.
Further, in order to improve the number of analyzes per unit time (throughput) of automatic analysis, a large number of reaction cells used in the automatic analyzer are generally mounted on the automatic analyzer. Therefore, when solving the above two problems, it is necessary that a plurality of cells can be hydrophilized simultaneously or sequentially. In addition, in order to improve the accuracy and reproducibility of analysis, it is required that the treated region of the reaction cell surface has a uniform hydrophilic property and suppresses processing variations between reaction cells.

  The present invention aims to meet these needs.

  To solve these problems, the inner walls of multiple reaction cells must be hydrophilized simultaneously or sequentially, but the hydrophilized region is limited to the height required for spectroscopic analysis from the bottom of the reaction cell. There must be. Effective means for hydrophilizing the surface of the synthetic resin include candidates such as oxygen plasma treatment, ozone treatment, ozone water treatment, corona discharge treatment, and UV treatment. However, these are all suitable for the purpose of processing an object having a planar shape, and are simple enough to achieve the purpose in a single step with respect to the surface of a special three-dimensional structure (see FIG. 1) handled by this patent. In general, it is difficult to find a method. In addition, it is not easy to process by limiting the area. For example, Patent Document 3 describes the oxidation and hydrophilization of a plastic container by ozone treatment. However, in this method, the plastic container cannot be partially oxidized and the plastic container is partially limited. It cannot be hydrophilized. In addition, the surface of a special three-dimensional structure (see FIG. 1) as handled by this patent forms a closed space. In the above plasma processing, the plasma density is not constant in the closed space, and the surface of the cell inner wall is not fixed. It is not easy to process uniformly.

  Thus, the inventors have come up with an application of a corona discharge method in which an object is sandwiched between two electrodes for discharge treatment. In this method, corona discharge is generated between an external electrode surrounding a reaction cell block made of synthetic resin from the outside and a rod-shaped internal electrode inserted into each unit cell (see FIG. 4). At this time, since the external electrode surfaces are close to the outer front and back surfaces of the spectrophotometric surface of the cell, discharge is performed between the opposing rod-shaped electrodes, and both inner walls of the spectrophotometric surface are subjected to corona discharge treatment. In addition, by installing external electrodes on the gaps and the bottom surface of the unit cell, the corona discharge treatment can also be performed on the non-photometric surface and the bottom surface. Moreover, it is also possible to process a part or all of the cell outer wall as required. This time, the photometric surface of the inner wall of the reaction cell was the target of corona discharge treatment.

  Since the corona discharge treatment is performed in an atmosphere containing oxygen such as air, oxygen atoms are introduced into the surface of the synthetic resin. Oxygen atoms are introduced into the surface of the synthetic resin in the form of hydroxyl groups, ether groups, carbonyl groups, and carboxyl groups. Since these are all hydrophilic functional groups, the hydrophilicity of the original synthetic resin surface with high hydrophobicity Will improve. The hydrophilicity of the surface of the synthetic resin was measured by a decrease in the contact angle of water, but it was found that the inner wall of the cell block subjected to the corona discharge treatment by the above method had a decreased contact angle and improved hydrophilicity. Moreover, the introduction state of oxygen atoms could be confirmed from the measurement result of XPS (X-ray photoelectron spectrum).

  In addition, since the discharge occurs only in the region where the inner and outer electrodes face each other, there is a possibility that the processing region can be limited. In fact, by optimizing the arrangement and shape of the electrodes to be inserted inside the cell, and by optimizing the height of the counter electrode arranged outside the cell, the hydrophilic area is only the area where the electrodes face each other, that is, the area where corona discharge occurs. It was confirmed that it can be limited to. That is, only the inner wall surface from the bottom of the reaction cell made of transparent synthetic resin to a predetermined height can be hydrophilized by corona discharge treatment. By utilizing the property that corona discharge is likely to occur when the distance between the electrodes is short, and the fact that discharge is likely to occur if there is a protruding structure on the electrode surface, a cell surface with uniform hydrophilicity in the surface is built, and at the same time Uniformity between cell lots can be improved.

  The hydrophilicity of the corona discharge-treated surface is based on the hydroxyl group, ether group, carbonyl group, and carboxyl group introduced by the treatment, but if the treatment conditions are strengthened, the higher-level oxide peroxide (peroxide) Was also found to produce.

  As described above, it is common that a large number of reaction cells are used in the automatic analyzer. According to the present invention, a plurality of cells can be hydrophilized simultaneously or sequentially by corona discharge, the properties of the treated regions are uniform, and the processing variation between cells can be reduced. Note that the present invention can be applied to either a plurality of cells or a single cell.

  The cell subjected to the corona discharge treatment has no change in appearance, has sufficient transparency in the wavelength range of 300 nm to 800 nm necessary for spectroscopic analysis, and has no adverse effect on the optical characteristics.

  As described above, according to the present invention, it is possible to carry out a stable hydrophilic treatment on the inner wall of a reaction cell for an automatic analyzer with a limited area. Moreover, according to the electrode and the manufacturing method of the present invention, the rise of the corona discharge is uniform, and the hydrophilicity uniformity of the treated cell surface and the uniformity among the treated cell lots are high. Further, even after a large number of cells are processed, they can be processed and manufactured stably and uniformly. Accordingly, it is possible to provide an automatic analyzer that does not cause the problem of bubble adhesion in stirring, solves the problem of cross-contamination between cells, and realizes clinical chemistry tests with high reliability and reproducibility.

  According to the present invention, the cell inner wall can be subjected to a hydrophilic treatment only in the region close to the cell closing portion of the spectrophotometric surface that does not like bubble adsorption, and the region closer to the opening than that of the cell inner wall is made hydrophobic. Can be held as is. In addition, the hydrophilicity and oxygen concentration of the treated area on the cell surface are kept uniform in the area, and there is little variation in the hydrophilicity and oxygen concentration of the treated area between lots. For this reason, the change in spectral transmittance due to bubble adsorption does not occur, and the accuracy and reproducibility of measurement data are improved. In addition, the hydrophobicity of the cell opening region prevents wetting of the reagent and sample, thereby preventing cross-contamination of samples between reaction cells and improving data reliability. These effects contribute to the miniaturization of samples and reagents, and also contribute to reducing the running cost of the automatic analyzer.

EXAMPLES Next, although an Example demonstrates this invention in detail, this invention is not limited to the following Example.
Example 1 Local Hydrophilization by Corona Discharge Treatment-Part 1-
A reaction cell for an automatic analyzer (hereinafter referred to as “cell”) was produced by injection molding using polycycloolefin as a raw material. Incidentally, the cell material may be one selected from polycycloolefin, polycarbonate resin, acrylic resin, and polystyrene resin. It is desirable to select a polycycloolefin from the viewpoint of low water absorption, low moisture permeability, high total light transmittance, low refractive index, and low mold shrinkage.

  In this embodiment, a cell block formed by integrally molding four single cells was used. FIG. 1 shows a perspective external view of a cell block. The molded cell block 50 includes four single cells 51. The long side 101 of the cell block 50 is 60 mm, the short side 102 is 10 mm, and the height 103 is 40 mm. When the single cell 51 is mounted on the automatic analyzer, the reaction progress and the reaction result of the sample and the reagent are measured by the spectrum. Each single cell has two surfaces (photometry surfaces) through which measurement light is transmitted and a non-photometry surface through which measurement light is not transmitted. FIG. 2 is a cross-sectional view of a single cell divided into two along the long axis of the non-photometric surface. The single cell includes a non-photometric surface outer wall portion 111, a non-photometric surface inner wall portion 112, a photometric surface outer wall portion 113, a photometric surface inner wall portion 114, and a bottom surface 115. The details are shown in FIG. The dimension of the inner wall portion of the single cell is such that the half length 116 of the non-photometric surface is 3 mm, the length 117 of the photometric surface is 4 mm, the height 118 is 30 mm, the single cell thickness 150 is 1 mm, An opening 140 is provided.

  500 μl of ethanol was injected into all the single cells 51 and left for 24 hours. After removing the ethanol, the inner wall surface of the single cell was cleaned by placing in a vacuum desiccator and drying. Next, corona discharge local treatment was performed. In addition, you may perform a corona discharge local process, without performing the cleaning of the inner wall surface by the said ethanol.

  FIG. 4 shows a schematic diagram of the corona discharge local treatment. The photometric surfaces of the four single cells 51 of the cleaned and dried cell block 50 were sandwiched between the cathode plates 218. The cathode plate is connected to the ground 217 via the wiring 216.

  By adjusting the height of the cathode plate, the height of the corona discharge treatment surface of the cell inner wall can be limited. Further, a dielectric or an insulator may be inserted between the cathode plate and the cell. Further, the cathode plate and the cell may be in close contact with each other, or may be separated by an appropriate distance.

  In this example, the height of the cathode plate was determined so that the inner wall from the bottom surface of each single cell to 14 mm was processed. Thereafter, a corona discharge rod-shaped (cylindrical) electrode 214 was placed inside each single cell 51 from the bottom to a height of 1 mm toward the center of the bottom of each single cell. The diameter of the corona discharge rod-like electrode 214 is 2 mm at the maximum and the length is 50 mm, and is connected to the corona discharge source 211 via the anode 213 and the wiring 212. As the corona discharge power source, polydyne manufactured by Navitas was used. Next, a corona discharge treatment was applied to the desired height of the inner wall of the single cell by applying a voltage of 6 kV in the atmosphere. FIG. 5 shows a state in which the configuration around the electrode at this time is viewed from the direction of the arrow 219. In order to maintain hydrophilic uniformity in the in-plane region of the photometric surface subjected to corona discharge treatment and uniformity between cells subjected to simultaneous treatment, discharge treatment was performed with the following configuration.

  A rod-shaped electrode 214 was inserted into the cell 51. The rod-like electrode is made of metal and may be prismatic or cylindrical. In this embodiment, a stainless steel cylindrical electrode was used. The rod-shaped electrode 214 includes a region 601 having a large electrode diameter and a region 602 having a small electrode diameter. The heights of the counter electrodes 61 and 62 were adjusted to be the same height as the boundary line between the region 601 and the region 602. By making the distance 632 from the cell bottom to the upper end of the counter electrode equal to the distance 631 from the cell bottom to the electrode boundary line, the cell inner wall desired to be processed was processed. In this embodiment, the distances 631 and 632 are 14 mm. Note that the electrode edge of the region 601 may be chamfered with a radius of about R0.5 mm.

  In general, the law is used in which the corona discharge energy increases as the distance between the electrodes decreases. Since the region with a large electrode diameter is closer to the counter electrode than the region with a small electrode diameter, corona discharge is likely to occur and the discharge energy is high. Accordingly, corona discharge is preferentially generated from the region 601 that is close to the counter electrode toward the counter electrode. At this time, since the distance 631 is equal to the distance 632 as described above, the region where discharge is desired can be uniformly processed. Moreover, it was possible to suppress the area to be processed in an ambiguous manner, and it was considered that there was a clear difference between the area subjected to the corona discharge treatment on the cell inner wall surface and the untreated area. The electrode diameter of the electrode region 601 used in this example was 2 mm, the electrode diameter of the region 602 was 1 mm, and the region 601 did not exceed the cell width 610.

  Disposing the rod-shaped electrode so as to be at the center of the cell bottom and making the distance 613 and the distance 614 between the rod-shaped electrode and the cell photometric surfaces 301 and 302 equal to each other can achieve uniformity and reproducibility of the two photometric surfaces. is important. Also, when the distance 611 between the cell photometric surface 301 and the counter electrode 61 and the distance 612 between the cell photometric surface 302 and the counter electrode 62, making the distances 611 and 612 equal makes the uniform processing and reproducibility of the two photometric surfaces. It is important for certain processes. In this embodiment, the distances 611 and 612 are made equal to 2 mm. The distance 621 and the distance 622 between the region 602 and the cell are made equal.

If the difference between the distances 611 and 612 is within 2 mm, there is no problem in uniform processing of the two photometric surfaces. In addition, if the difference between the distances 613 and 614 is within 1 mm, it was confirmed that there is no problem in uniform processing of the two photometric surfaces.
At this time, if a cathode plate is provided on the bottom outer wall of the reaction cell or the outer wall of the non-photometric surface, corona discharge treatment can be performed on the bottom surface or non-photometric surface of the reaction cell. That is, the corona discharge treatment position can be limited by the position where the cathode plate is installed. In this embodiment, only the counter electrodes 218 and 219 are arranged.

  FIG. 6 shows a cross-sectional perspective external view of a single cell after the corona discharge local treatment by the above method. Corona discharge treatment could be performed on the portion 120 from the bottom surface 115 to the boundary line 119 in the photometric surface inner wall portion 114 of the cell 51. At this time, with the boundary line 119 as a boundary, the closed portion 130 side became hydrophilic and the opening portion side became hydrophobic, and there was a clear difference in hydrophilicity. At this time, the corona discharge local treatment could be similarly performed on the inner wall portion of the surface opposite to the photometric surface shown in the figure. Similar corona discharge local treatment could be performed simultaneously on all of the plurality of single cells provided in the cell block.

  In addition, by installing the cathode plate not only on the photometric surface but also on the non-photometric surface and the bottom surface, the corona discharge treatment can be performed on the non-photometric surface and the bottom surface. In Examples 1 to 6 below, an example is shown in which a cell in which only the photometric surface is subjected to corona discharge treatment is prepared. It should be noted that detection bubbles can be eliminated if bubbles do not adhere to a region (photometry unit) through which light is transmitted when measuring a spectral spectrum.

  Table 1 shows the contact angle of water according to the distance from the cell bottom with respect to the photometric surface inner wall surface in the cell. The corona discharge treatment time is 10 seconds, but if the result of optimization is 1 second to 20 seconds, the same result is obtained.

For measurement of the contact angle, Drop Master 500 manufactured by Kyowa Interface Science was used. Using a syringe, 1 μl of pure water was dropped onto the treated cell surface, and the static contact angle 0.5 seconds after the landing was measured by the θ / 2 method. For the measurement, six treated samples were prepared, and measurement was performed at intervals of 1 mm to 2 mm from the cell bottom of the photometric surface inner wall surface, and an average value among the six samples was obtained.
As a result, when the distance from the cell bottom was 15 mm or more, the result was the same as the cell surface before the corona discharge treatment, and the contact angle with water was 89 to 91 degrees. On the other hand, when the distance from the cell bottom, which is the region where treatment was desired, was between 1 mm and 13 mm, the contact angle with water was reduced to about 40 degrees by the corona discharge treatment. Thus, it was confirmed that the corona discharge treatment can be selectively performed. That is, hydrophilicity can be imparted by limiting the area on the cell surface by corona discharge treatment. There was a clear difference in hydrophilicity at a distance of 14 mm from the cell bottom.

  Next, elemental analysis of the corona discharge treated surface was performed by XPS (X-ray photoelectron spectroscopy), and Table 2 shows the oxygen atom abundance ratio (%). The oxygen atom abundance ratio is hereinafter also referred to as oxygen concentration. Hereinafter, for the measurement, a SHIMADZU-CRATOS X-ray photoelectron spectroscopy (XPS) apparatus is used. In order to compare the atomic ratio of carbon, oxygen, and nitrogen, the pass energy is set to 20 eV in the range of 1400 eV to -20 eV. A wide scan was performed.

  As shown in Table 2, when the distance from the cell bottom was 15 mm or more, as in the cell surface before the corona discharge treatment, the oxygen atom abundance was 0 atomic% below the detection lower limit. On the other hand, when the distance from the cell bottom, which is the region where treatment was desired, was between 1 mm and 13 mm, the oxygen atom abundance ratio was 12 atom% on average. Oxygen is introduced by corona discharge treatment, and the polycycloolefin is oxidized and hydrophilized.

  Next, the uniformity within the processing surface and the uniformity among the processed cell lots will be described. As a result of measuring the contact angle of each of the 10 cells treated by the above method (6 locations), the average contact angle from the cell bottom to 14 mm was 40 degrees and the standard deviation (σ) was 1 degree. . In addition, when the sum of the average value of the contact angle of the hydrophilic region and the standard deviation (σ) was 85 degrees or less, it was confirmed that the hydrophilic cell had sufficient properties as a reaction cell for an automatic analyzer. Similarly, as for the variation in oxygen concentration in the cell hydrophilic region, as a result of XPS measurement, the average value was 12 atomic%, and the standard deviation (σ) was about 0.6 atomic%.

  From the viewpoint of reducing the contact angle shown in Table 1 and from the viewpoint of the oxygen atom abundance ratio of XPS shown in Table 2, it can be seen that the uniformity of hydrophilicity in the region desired to be treated is high. The uniformity among the processed cell lots was also confirmed.

  Next, as a result of examining the presence or absence of bubble adhesion when 150 μl of pure water was poured into a cell subjected to corona discharge treatment, bubble adhesion did not occur. Therefore, it was confirmed that a stable hydrophilization treatment was possible by performing a corona discharge treatment on a part of the cell inner wall. Further, the contact angle of the portion not subjected to the corona discharge treatment remained 90 degrees, which was the same as that of the cell surface not subjected to the corona discharge treatment. That is, the inner wall of the reaction cell could be selectively subjected to corona discharge treatment, and a reaction cell having a stable hydrophilic portion and hydrophobic portion on the inner wall portion could be produced.

  Next, the presence or absence of bubbles was examined when 150 μl of water was injected into the cell after the cell treated with corona discharge for 10 seconds was left at room temperature. Table 3 shows the number of elapsed days and the presence or absence of bubbles after the passage of days.

  When 150 μl of water was injected into the cell at 0 and 60 days, it was confirmed that no bubbles were attached and no bubbles were attached even after 120 days and 180 days. Therefore, the reaction cell prepared according to the present invention can be used even after long-term storage.

  The reaction cell of this example was confirmed as a reaction cell for an autoanalyzer, which does not cause bubble adhesion, has stirring stability and transparency, and can prevent cross-contamination of samples and reagents between the cells. .

Further, the corona discharge treatment shown in FIG. 4 can be applied to other shapes of cell blocks. As shown in FIG. 7, in the cell block 90 in which a plurality of cells 91 share the photometric surface 92, the outer wall of the region to be hydrophilized on the photometric surface is sandwiched between cathode plates 218, so that the height of the corona discharge treatment surface of the cell inner wall is increased. The corona treatment can be performed by limiting the thickness. By making the photometric surface hydrophilic, it is possible to carry out stable measurement without bubbles adhering when light is transmitted through the photometric region and a solution is detected. It can be implemented by optimizing the electrode arrangement, electrode shape, and interelectrode distance as described above, and a similar reaction cell can be produced.
<Example 2> Local hydrophilization by corona discharge treatment-Part 2-
Similar to Example 1, the cell inner wall was locally hydrophilized by corona discharge treatment. The rod-shaped electrode 214 used was a columnar one as in Example 1, and the electrode diameter of the region 602 was set to 1 mm as in Example 1. In Example 2, an electrode having a mountain-shaped region 603 as shown in FIG. 8 is used as the region 601 having a large electrode diameter. In general, local protrusions are more prone to electric field concentration and corona discharge intensity is stronger than flat structures, so the discharge rise timing does not vary between the processed cell lots, and the hydrophilicity of the processed cells varies between the cell lots. Absent. In this embodiment, the groove depth 641 is set to 0.3 mm, and the pitch (groove interval) 642 is set to 0.5 mm. FIG. 9 shows a part of the cross-sectional line in FIG. 8A-A ′. The groove depth and pitch are not limited to the above, and various groove depths and pitches can be combined. By using the same electrode arrangement, insertion position, and inter-electrode distance as in Example 1, the closed surface side of the cell surface was hydrophilic and the open side was hydrophobic, and there was a clear difference in hydrophilicity. Similar corona discharge local treatment could be performed simultaneously on all of the plurality of single cells provided in the cell block. By using the chevron-shaped electrode, it was possible to reduce the discharge lot-to-lot variation, and when the treated cell was evaluated, it was possible to reduce the contact angle variation and the oxygen concentration variation as in Example 1.

  Further, the corona discharge treatment shown in FIG. 4 can be applied to other shapes of cell blocks. As shown in FIG. 7, in the cell block 90 in which a plurality of cells 91 share the photometric surface 92, the outer wall of the region to be hydrophilized on the photometric surface is sandwiched between cathode plates 218, so that the height of the corona discharge treatment surface of the cell inner wall is increased. The corona treatment can be performed by limiting the thickness. By making the photometric surface hydrophilic, it is possible to carry out stable measurement without bubbles adhering when light is transmitted through the photometric region and a solution is detected. It can be carried out by setting the electrode arrangement, the electrode shape, and the distance between the electrodes as described above, and a similar reaction cell can be produced.

The reaction cell of this example was confirmed as a reaction cell for an autoanalyzer, which does not cause bubble adhesion, has stirring stability and transparency, and can prevent cross-contamination of samples and reagents between the cells. .
<Example 3> Local hydrophilization by corona discharge treatment-Part 3-
Similar to Example 1, the cell inner wall was locally hydrophilized by corona discharge treatment. The rod-shaped electrode 214 used was a columnar one as in Example 1, and the electrode diameter of the region 602 was set to 1 mm as in Example 1. In Example 3, an electrode having an iris region 604 as shown in FIG. 10 is used for the region 601 having a large electrode diameter. In general, local protrusions are more prone to electric field concentration and corona discharge intensity is stronger than flat structures, so the discharge rise timing does not vary between the processed cell lots, and the hydrophilicity of the processed cells varies between the cell lots. Absent. A grid-like or mesh-like notch as shown in FIG. 9 is generally used because it can be achieved by knurling.

  FIG. 11 is a schematic diagram in which a part of the cross section is represented by a line indicated by A-A ′ in FIG. 10. In this embodiment, the groove depth 651 is set to 0.3 mm, and the pitch (groove interval) 652 is set to 0.5 mm. FIG. 12 shows a schematic diagram in which a part of the cross section is represented by a line indicated by B-B ′ in FIG. 9. In this embodiment, the groove depth 653 is set to 0.3 mm, and the pitch (groove interval) 654 is set to 0.5 mm. The groove depth and pitch are not limited to the above. By using the same electrode arrangement, insertion position, and inter-electrode distance as in Example 1, the closed surface side of the cell surface was hydrophilic and the open side was hydrophobic, and there was a clear difference in hydrophilicity. Similar corona discharge local treatment could be performed simultaneously on all of the plurality of single cells provided in the cell block. As in Example 2, the use of the iris electrode having protrusions on the electrode surface can reduce the discharge lot-to-lot variation, and the treated cell was evaluated. As in Example 1, the contact angle variation and The variation of oxygen concentration was reduced.

  Further, the corona discharge treatment shown in FIG. 4 can be applied to other shapes of cell blocks. As shown in FIG. 7, in the cell block 90 in which a plurality of cells 91 share the photometric surface 92, the outer wall of the region to be hydrophilized on the photometric surface is sandwiched between cathode plates 218, so that the height of the corona discharge treatment surface of the cell inner wall is increased. The corona treatment can be performed by limiting the thickness. By making the photometric surface hydrophilic, it is possible to carry out stable measurement without bubbles adhering when light is transmitted through the photometric region and a solution is detected. It can be carried out by setting the electrode arrangement, the electrode shape, and the distance between the electrodes as described above, and a similar reaction cell can be produced.

The reaction cell of this example was confirmed as a reaction cell for an autoanalyzer, which does not cause bubble adhesion, has stirring stability and transparency, and can prevent cross-contamination of samples and reagents between the cells. .
Example 4 Local Hydrophilization by Corona Discharge Treatment—Part 4—
Similar to Example 1, the cell inner wall was locally hydrophilized by corona discharge treatment. The rod-shaped electrode used is shown in FIG. A cylindrical rod-like electrode 70 is used, and a hollow region 702 having a diameter of 0.1 mm and a suction port 701 are provided. The electrode diameter used in this example was an electrode having a large electrode region 704 and a small electrode region 705 as in Example 1. In this embodiment, if there are a hollow region and a suction port, a straight type may be used with one type of electrode diameter. Similar to Example 1, an appropriate electrode arrangement, an appropriate insertion position, and an appropriate interelectrode distance were used. Further, a plasma generated by corona discharge is created by using a diaphragm pump at the time of discharge to draw air at a flow rate of 20 cc / min through a suction port and a hollow region, thereby creating an air flow in the direction indicated by arrow 703. Was not allowed to protrude from the desired treatment area on the cell surface. As a result, the closed surface side of the cell surface became hydrophilic and the open side was hydrophobic, and there was a clear difference in hydrophilicity. Similar corona discharge local treatment could be performed simultaneously on all of the plurality of single cells provided in the cell block. As a result, variation between discharge lots could be reduced, and the cells after treatment were evaluated. As in Example 1, variation in contact angle and variation in oxygen concentration could be reduced. In addition, the said flow rate can be implemented in the range of 1 cc / min-200 cc / min.

  Further, the corona discharge treatment shown in FIG. 4 can be applied to other shapes of cell blocks. As shown in FIG. 7, in the cell block 90 in which a plurality of cells 91 share the photometric surface 92, the outer wall of the region to be hydrophilized on the photometric surface is sandwiched between cathode plates 218, so that the height of the corona discharge treatment surface of the cell inner wall is increased. The corona treatment can be performed by limiting the thickness. By making the photometric surface hydrophilic, it is possible to carry out stable measurement without bubbles adhering when light is transmitted through the photometric region and a solution is detected. It can be carried out by setting the electrode arrangement, the electrode shape, and the distance between the electrodes as described above, and a similar reaction cell can be produced.

The reaction cell of this example was confirmed as a reaction cell for an autoanalyzer, which does not cause bubble adhesion, has stirring stability and transparency, and can prevent cross-contamination of samples and reagents between the cells. .
<Example 5> Local hydrophilization by corona discharge treatment-Part 5-
Similar to Example 1, the cell inner wall was locally hydrophilized by corona discharge treatment. The rod-shaped electrode used is shown in FIG. A cylindrical rod-shaped electrode 80 was used. The electrode diameter used in this example was an electrode having a large and small electrode diameter as in Example 1. In this embodiment, a straight type may be used with one type of electrode diameter. Similar to Example 1, an appropriate electrode arrangement, an appropriate insertion position, and an appropriate interelectrode distance were used. Furthermore, a mask 81 made of the same material resin as the cell is arranged in the area where the treatment is not desired on the cell inner wall surface so that the plasma produced by corona discharge does not protrude from the desired treatment area on the cell surface. . As a result, the same effect as in Example 1 was obtained, and the closed side of the cell surface was hydrophilic and the open side was hydrophobic, and there was a clear difference in hydrophilicity. Similar corona discharge local treatment could be performed simultaneously on all of the plurality of single cells provided in the cell block. As a result, variation between discharge lots could be reduced, and the cells after treatment were evaluated. As in Example 1, variation in contact angle and variation in oxygen concentration could be reduced.

  Moreover, not only the position of the above-mentioned mask but also a portion that is not desired to be subjected to corona discharge treatment can be treated in a limited manner by covering it with a mask made of the same material as the reaction cell in advance and then performing corona discharge treatment. is there.

  Further, the corona discharge treatment shown in FIG. 4 can be applied to other shapes of cell blocks. As shown in FIG. 7, in the cell block 90 in which a plurality of cells 91 share the photometric surface 92, the outer wall of the region to be hydrophilized on the photometric surface is sandwiched between cathode plates 218, so that the height of the corona discharge treatment surface of the cell inner wall is increased. The corona treatment can be performed by limiting the thickness. By making the photometric surface hydrophilic, it is possible to carry out stable measurement without bubbles adhering when light is transmitted through the photometric region and a solution is detected. It can be carried out by setting the electrode arrangement, the electrode shape, and the distance between the electrodes as described above, and a similar reaction cell can be produced.

  The reaction cell of this example was confirmed as a reaction cell for an autoanalyzer, which does not cause bubble adhesion, has stirring stability and transparency, and can prevent cross-contamination of samples and reagents between the cells. .

  In addition, you may apply the partial limitation processing method by a mask like this Example 5 in the case of the electrode shape of Examples 1-4.

Further, as shown in FIG. 15, in addition to the above embodiment, the discharge region can be limited by covering a part of the rod-shaped electrode 80 with a mask 82 made of a thick insulating resin. This method of covering the rod-shaped electrode with a mask can also be used in Examples 1 to 4, and is effective for partial treatment of the cell surface.
<Example 6> Example in an automatic analyzer An example of automatic analysis using the reaction cells prepared in Examples 1 to 5 will be described. In this example, an example using the reaction cell prepared in Example 1 will be described. In addition, you may use 1 type or multiple types of the reaction cell produced in Examples 1-5 simultaneously.

  FIG. 16 is a diagram showing a configuration example of the automatic analyzer according to the present invention, and the basic operation will be described next. Reference numeral 1 denotes a sample storage unit mechanism, in which one or more sample cells 25 are arranged. Here, an example of a sample disk mechanism that is a sample storage unit mechanism mounted on a disk-shaped mechanism unit will be described. However, as another form of the sample storage unit mechanism, a sample generally used in an automatic analyzer It may be in the form of a rack or sample holder. The sample here refers to a solution to be inspected used for reaction in the reaction cell, and may be a collected specimen stock solution or a solution obtained by subjecting it to a processing such as dilution or pretreatment. . The sample in the sample cell 25 is extracted by the sample nozzle 27 of the sample supply dispensing mechanism 2 and injected into a predetermined reaction cell. Reference numeral 5 denotes a reagent disk mechanism. This mechanism 5 includes a large number of reagent containers 6. The mechanism 5 is provided with a reagent supply dispensing mechanism 7, and the reagent is sucked and injected into a predetermined reaction cell by the reagent nozzle 28 of the mechanism 7. Reference numeral 10 denotes a spectrophotometer, and 26 denotes a light source with a condensing filter. Between the spectrophotometer 10 and the light source 26 with a condensing filter, a reaction disk 3 that accommodates a measurement target is disposed. On the outer periphery of the reaction disk 3, for example, 120 reaction cells 4 having a hydrophilic portion and a hydrophobic portion on the inner wall portion are installed. This hydrophilic portion is limited to the closed portion side of the reaction cell, but has an area sufficiently including the photometric region. On the other hand, the hydrophobic portion is on the opening side of the reaction cell, and prevents wetting due to the capillary action of the solution. Further, the entire reaction disk 3 is held at a predetermined temperature by a thermostatic chamber 9. Reference numeral 11 denotes a reaction cell cleaning mechanism, and the cleaning agent is supplied from the cleaning agent container 13. Reference numeral 19 is a computer, 23 is an interface, 18 is a Log converter and A / D converter, 17 is a reagent pipetter, 16 is a washing water pump, and 15 is a sample pipettor. Reference numeral 20 denotes a printer, 21 denotes a CRT, 22 denotes a floppy (registered trademark) disk or hard disk as a storage device, and 24 denotes an operation panel. The sample disk mechanism is controlled and driven by the driving unit 200, the reagent disk mechanism is driven by the driving unit 201, and the reaction disk is controlled and driven by the driving unit 202, respectively. Each part of the automatic analyzer is controlled by a computer via an interface.

  In the above configuration, the operator inputs analysis request information using the operation panel 24. The analysis request information input by the operator is stored in a memory in the microcomputer 19. The sample to be measured, which is put in the sample cell 25 and set at a predetermined position in the sample disk storage unit mechanism 1, is in accordance with the analysis request information stored in the memory of the microcomputer 19 and the sample pipettor 15 and the sample supply dispensing mechanism. A predetermined amount is dispensed into the reaction cell by the two sample nozzles 27. The sample nozzle 27 is washed with water. A predetermined amount of reagent is dispensed into the reaction cell by the reagent nozzle 28 of the reagent supply dispensing mechanism 7. After the reagent nozzle 28 is washed with water, it dispenses a reagent for the next reaction cell. The mixed solution of the sample and the reagent is stirred by the stirring rod 29 of the stirring mechanism 8 or the ultrasonic element. The stirring mechanism 8 sequentially stirs the liquid mixture in the next reaction cell. If a reaction cell composed of a hydrophilic part and a hydrophobic part is used, the bubbles encased by agitation will not be adsorbed to the photometric region on the inner wall surface of the cell, so that analysis data will not be affected.

  The reaction cell 4 is maintained at a constant temperature by a thermostat 9 and serves as both a reaction and a photometric container. In the reaction process, light is supplied from a light source 26 with a condensing filter, and the hydrophilic portion of the reaction cell is measured by a spectrophotometer 10 at regular intervals and mixed using one or more set wavelengths. The absorbance of the liquid is measured. By using a light source with a condensing filter at the time of measurement, only the hydrophilic portion of the reaction cell can be selectively transmitted.

  Since the bubble adhesion does not occur in the hydrophilic part of the reaction cell, there is little variation in absorption measurement and the accuracy is high. Similarly, since there is a hydrophilic portion on the inner wall portion of the reaction cell, bubbles that become a detection hindrance are not adsorbed on the photometric surface and bottom surface of the reaction cell, so that the region through which light passes through the reaction cell can be set near the bottom surface. Therefore, the amount of sample and reagent put into the reaction cell can be greatly reduced, which is useful from the viewpoint of reducing the running cost of the user. By using the reaction cell of the present invention, the amount of the reaction solution including the reagent and the sample solution can be reduced to 1/2 or less than the conventional amount, and automatic analysis can be performed.

  The measured absorbance is taken into the computer 19 via the Log converter and A / D converter 18 and the interface 23. The absorbed absorbance is converted into a concentration value, and the concentration value is stored in a floppy (registered trademark) disk or hard disk 22 or output to the printer 20. In addition, inspection data can be displayed on the CRT 21. The reaction cell 4 that has been measured is washed with water by a reaction cell washing mechanism (nozzle arm) 11. After the washing is completed, water is sucked by the suction nozzle 12 and then used sequentially for the next analysis.

  Thus, as a result of mounting the reaction cell 4 having a hydrophilic portion and a hydrophobic portion on the inner wall portion and performing automatic analysis, there was no phenomenon in which the test solution climbed to the opening of the reaction cell by capillary action. That is, cross-contamination and cross-contamination mixed with reagents in adjacent reaction cells did not occur. Moreover, since there was no bubble adsorption, the measurement error was reduced. On the other hand, cross-contamination and cross-contamination occurred when the inner wall of the reaction cell was made hydrophilic from the bottom to the opening.

  This example shows an example in which automatic analysis was performed when the amount of the reaction solution was minimized using a reaction cell in which a portion from the bottom surface of the inner wall of the photometric surface to a desired height was locally hydrophilized. However, the present invention is not limited to the size of the region to be hydrophilized or the amount of the reaction solution. In addition, if the reaction cell has a high hydrophilicity on the inner wall portion of the photometric region, it is possible to carry out stable automatic analysis without causing bubbles and without causing cross-contamination and cross-contamination.

  Furthermore, when water is poured into the reaction cell, the hydrophilicity of the hydrophilic portion of the cell can be further increased, and a more stable analysis can be performed. The water used for water injection here may be pure water, but is not limited to pure water, and may be a solution to which an additive having an effect of further improving hydrophilicity is added. In order to obtain the same effect, not only liquid but also fine powder, mist, or gas may be used. Therefore, it is desirable to use an automatic analyzer after the reaction cell is immersed in water.

  As described above, the reaction cell produced by the production method of the present invention using the electrode of the present invention is mounted on an automatic analyzer and useful for automatic analysis.

The perspective external view of a cell block. The perspective external view of a division cell. The perspective external view of a division cell. The schematic diagram of corona discharge local treatment. The cross-sectional schematic diagram of a corona discharge local process. The perspective external view of the division | segmentation cell after a corona discharge local process. The schematic diagram of corona discharge local treatment. Electrode external view. FIG. Electrode external view. FIG. FIG. The cross-sectional schematic diagram of a corona discharge local process. The cross-sectional schematic diagram of a corona discharge local process. The cross-sectional schematic diagram of a corona discharge local process. The figure which shows the structural example of an automatic analyzer.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Sample storage part mechanism, 2 ... Dispensing mechanism for sample supply, 3 ... Reaction disk, 4 ... Reaction cell, 5 ... Reagent disk mechanism, 6 ... Reagent container, 7 ... Dispensing mechanism for reagent supply, 8 ... Stirring mechanism , 9 ... Thermostatic bath, 10 ... Spectrophotometer, 11 ... Reaction cell washing mechanism, 12 ... Suction nozzle, 13 ... Cleaning agent container, 15 ... Sample pipetter, 16 ... Washing water pump, 17 ... Reagent pipettor, 18 ... Log converter and A / D converter, 19 ... computer, 20 ... printer, 21 ... CRT, 22 ... floppy disk or hard disk, 23 ... interface, 24 ... operation panel, 25 ... sample cell, 26 ... collection Light source with optical filter, 27 ... sample nozzle, 28 ... reagent nozzle, 29 ... stirring rod, 50 ... cell block, 51 ... single cell, 61 ... counter electrode, 62 ... counter electrode, 70 ... Electrode, 80 ... Electrode, 81 ... Mask, 82 ... Mask, 90 ... Cell block, 91 ... Cell, 92 ... Photometric surface, 101 ... Long side, 102 ... Short side, 103 ... Height, 111 ... Non-photometric surface outer wall, 112 ... Non-photometric surface inner wall, 113 ... Photometric surface outer wall, 114 ... Photometric surface inner wall, 115 ... Bottom surface, 116 ... Half length of non-photometric surface, 117 ... Length of photometric surface, 118 ... Inner wall height, 119 ... Boundary line, 120 ... corona discharge treatment part, 130 ... closing part, 140 ... opening part, 150 ... single cell thickness, 160 ... region, 161 ... boundary line, 162 ... boundary line, 200 ... drive part, 201 ... drive part , 202, driving unit, 211, corona discharge source, 212, wiring, 213, anode, 214, electrode, 216, wiring, 217, ground, 218, cathode plate, 219, arrow, 301, photometry surface, 302, photometry surface , 601... Region, 60 ... area, 603 ... area, 604 ... area, 610 ... cell width, 611 ... distance, 612 ... distance, 613 ... distance, 614 ... distance, 621 ... distance, 622 ... distance, 631 ... distance, 632 ... distance, 641 ... Depth, 642 ... pitch, 651 ... depth, 652 ... pitch, 653 ... depth, 654 ... pitch, 701 ... suction port, 702 ... hollow area, 703 ... arrow, 704 ... area, 705 ... area.

Claims (8)

  An electrode for hydrophilizing the inner wall surface of a cell, an electrode plate is arranged outside the cell facing the inner wall surface to be hydrophilized except for the vicinity of the opening of the cell, and an electrode rod is arranged inside the cell Discharge electrode.   2. The electrode according to claim 1, wherein a diameter of an electrode bar portion facing an electrode plate arranged outside the resin cell is larger than other portions of the electrode bar.   3. The electrode according to claim 2, wherein the electrode has a protruding shape at a portion where the electrode diameter is large.   The electrode according to claim 1 or 2, wherein the electrode bar has a hollow region.   In the method for producing a resin cell, the electrode exterior according to any one of claims 1 to 4 is inserted into the resin cell, and the cell exterior facing the inner wall surface to be hydrophilized excluding the vicinity of the opening of the cell And a step of corona discharge between the electrode and the electrode plate, and imparting hydrophilicity to the inner wall surface facing the region covered by the plate electrode plate, A method for manufacturing a resin cell.   The method for manufacturing a resin cell according to claim 5, wherein the cell is for an automatic analyzer.   In the method for producing a resin cell, the step of inserting the electrode according to claim 4 into the cell and covering the outside of the cell facing the inner wall surface to be hydrophilized excluding the vicinity of the opening of the cell with an electrode plate And a step of corona discharge between the electrode and the electrode plate, and at the time of corona discharge, atmospheric air inside the reaction cell is sucked from the hollow portion of the electrode and is opposed to a region covered by the plate electrode plate A method for producing a cell, comprising imparting hydrophilicity to an inner wall surface.   It is a manufacturing method of the resin-made cells of Claim 7, Comprising: The manufacturing method of the cell for automatic analyzers.

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