JP2005099040A - Vessel for immunoassay - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To eliminate loss of a reagent and a sample at preservation, dilution and reaction and enable high-sensitivity measurement by controlling a saturated adsorption amount of all molecules used in an analysis to a vessel to a fixed value or smaller through a study of characteristics of the vessel. <P>SOLUTION: The vessel for immunoassay provides a saturated adsorption amount of molecules used in an analysis of 1×10<SP>-1</SP>pmol/cm<SP>2</SP>or lower. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a container used for storage, dilution, and reaction of reagents and / or specimens in immunoassay for detecting antibodies or antigens using antigen-antibody reactions.

  In a conventional immunoassay, a container made of polystyrene or polypropylene is used for storing and diluting a reagent or specimen to be used, but there is nonspecific adsorption of molecules in the reagent or specimen to the container. The decrease in the reagent or specimen and the change in the concentration of the reagent or specimen solution will inevitably occur.

  In recent years, with the diversification of immunoassay methods, especially in the drug discovery departments of pharmaceutical manufacturers, there are many cases where natural substances are extracted, purified, and used, and such substances are generally very small and expensive, The decrease in reagent during the storage or dilution process due to adsorption cannot be ignored.

Containers for handling specimens are also used for collection of clinically important proteins such as albumin, transferrin, and immunoglobulin in specimens such as serum and urine used for clinical diagnosis before collection and measurement. Most of the containers used in each stage are adsorbed, such as syringes and cups at the collection stage, tubes at the storage stage, centrifuge tubes and test tubes at the purification, concentration and dilution stages. Is a non-surface-treated polypropylene or polystyrene, so even if the amount of adsorption at each stage is very small, the concentration change in the sample at the time of measurement is very large compared to the time of collection when considered in all steps Expected to be.
In addition, about 80% of the clinical test kit price that is generally sold in clinical test drug manufacturers is occupied by the price of the solid phase reagent, and the decrease in the reagent due to adsorption to the container. Suppressing it leads to a significant cost reduction.

On the other hand, in the container used for measurement, in the immunoassay method called the solid phase method, analysis is performed using the protein solid-phased on the surface of the container. A material that has been subjected to a so-called high adsorption treatment in which a saturated adsorption amount is increased by introducing a functional group and adjusting a hydrophilic-hydrophobic balance is used.
However, in recent years, analysis by an automatic analyzer (robot) has been developed for the purpose of shortening analysis time and mass analysis, and it is rapidly spreading especially in the drug discovery department of pharmaceutical manufacturers.

Here, in the measurement by the conventional solid phase immobilization method, a washing step for eliminating the excess molecules that are not solid phased is necessary, but the washing step of repeating the dispensing and aspiration of the washing liquid is difficult for the automatic analyzer. Therefore, a so-called sequential addition method that does not require separation of reactants and unreacted substances by a washing step is being developed as a measurement method suitable for an automatic analyzer.
In the sequential addition method, the molecule is not solid-phased during the reaction, and the reaction is performed in a solution. Therefore, in the container having the high adsorption treatment surface as described above, the reaction in the solution is hindered or the efficiency is lowered due to unnecessary adsorption.

Furthermore, due to recent advances in measurement technology, fluorescence and luminescence method evaluation techniques have been established that have higher sensitivity than conventional colorimetric absorbance measurements. Adsorption of the necessary molecules into the container is expected to become a major problem.
However, the containers currently used for them are still not considered for adsorption, and polystyrene or polypropylene, such as a material that only considers moldability, transparency, and low temperature resistance, is a surface for suppressing adsorption. It is used without treatment, and no approach has been made to solve the problem of reagent loss and sensitivity reduction from the direction of container characteristics.

However, several techniques have been studied and implemented so far to control non-specific adsorption on the surface of an immunoassay container.
For example, the most commonly performed method is a so-called blocking method in which a protein that is inactive to the measurement system is coated. This method basically utilizes non-specific adsorption of proteins. Therefore, the blocking effect tends to vary from coating to coating, and the effect is easily influenced by the state of the protein. Inactive proteins are only non-specifically adsorbed and thus easily released into the solution and cannot be used for storage. Patent Documents 1 and 2 disclose a technique for eliminating the above-mentioned liberation by chemically immobilizing proteins, but proteins are highly likely to undergo structural changes depending on drying, storage temperature and storage period. Therefore, versatility as an actual container could not be expected.

The adsorbed protein induces secondary adsorption by changing its higher order structure. In other words, proteins that are inactive in the free state cannot be maintained in a completely inactive state due to a change in higher-order structure in an adsorbed or chemically bound state, and direct adsorption to the substrate is impeded. However, there is a problem in that secondary adsorption between protein and protein occurs.
Since secondary adsorption between protein and protein varies depending on the type of protein, it is essential to select the optimal protein to be used for blocking for each system to be measured. In addition, a mixed solution of proteins such as serum is used as a sample. When used, there is no blocking protein that can control adsorption for all proteins.
JP-A-6-174726 JP-A-7-128336

  Therefore, the present inventor paid attention to the characteristics of the container, and as a result of intensive studies, if the saturated adsorption amount to the container was controlled below a certain value for all molecules used in the analysis, the reagent during storage, dilution and reaction The present invention has been completed by finding that high-sensitivity measurement is possible without any decrease in the number of specimens.

That is, the present invention provides an immunoassay container in which the amount of saturated adsorption of molecules used for analysis is 1 × 10 ⁻¹ pmol / cm ² or less.

The container for immunoassay of the present invention has no loss due to adsorption when storing or diluting reagents because the adsorption of molecules or serum used for measurement is 1 × 10 ⁻¹ pmol / cm ² or less. When used as a system container, high-sensitivity and high-accuracy measurement can be carried out without a decrease in reaction efficiency due to adsorption of measurement molecules or inhibition of reaction due to adsorption of unnecessary molecules.
Also, in clinical tests using serum, structural changes due to adsorption of serum components do not occur, so tests under conditions closer to the body are possible.

Conventionally, molecules of polystyrene or polypropylene containers used for containers for immunoanalysis, for example, protein adsorption amount is about 1 to 10 pmol / cm ² or more, and molecules in solution used for analysis, for example, proteins are solutions. Depending on the concentration and the contact area with the container, about 20% to 50% is adsorbed to the container. Here, if 20% to 50% of the adsorbed molecules are essential for the reaction in the solution, the reaction efficiency, that is, the measurement sensitivity will be reduced by 20% to 50%. Any substance that causes an unnecessary reaction due to structural changes will result in significant noise.

Therefore, a container in which molecules used for analysis are not adsorbed at all is ideal, but a sufficient effect can be obtained by substantially reducing the adsorption amount to 1/10 to 1/100 of the current amount.
In other words, the amount of molecules adsorbed in the solution varies depending on the type and temperature of the molecules, the solution concentration, the pH of the solvent, etc., but as a reaction vessel, the saturated adsorption amount of the molecules used for the analysis is the concentration, temperature, Under the condition of hydrogen ion concentration, it is 1 × 10 ⁻¹ pmol / cm ² or less. When using serum, serum diluted usually 1 to 10 times is used. If the saturation adsorption amount of molecules involved in and / or influence the analysis among the contained molecules is always 1 × 10 ⁻¹ pmol / cm ² or less under the temperature and hydrogen ion concentration conditions Good.

Similarly, for containers used for storage and dilution, the saturated adsorption amount of molecules used for storage and dilution is always 1 × 10 ⁻¹ pmol under the concentration, temperature and hydrogen ion concentration at which the reagent is removed from the storage container or diluted. / Cm ² or less is sufficient. In many cases, the reagent is stored at a low temperature of −80 ° C. However, since the adsorption is an equilibrium reaction, the saturated adsorption amount at the concentration, temperature, and hydrogen ion concentration when the reagent is removed from the storage container is 1 × 10 ^−3. It may be ¹ pmol / cm ² or less.

A more preferable saturated adsorption amount is 1 × 10 ⁻² pmol / cm ² or less, and particularly preferably 1 × 10 ⁻³ pmol / cm ² or less.
In addition, as a molecule | numerator used for an analysis here, protein (an enzyme, bioactive protein, an antibody, etc.), a nucleic acid, a bioactive substance, etc. are mentioned, However, Protein is especially preferable. The saturated adsorption amount can be measured by colloidal gold labeled immunoassay.

  The present invention has a great effect in addition to the features described above in that no protein is adsorbed. Normally, the structure of a protein changes when it is adsorbed. In immunoassay, the target protein is present in the measurement system, but it is not detected by the antibody for detection due to the structural change. There is a case. In addition, in clinical examinations and the like, it is necessary to examine serum in a state where it exists in a living body, but in actuality, examination in a state where structural changes have occurred due to adsorption is unavoidable. In the present invention, serum can be measured in a state closer to that in vivo in clinical tests without causing structural changes due to the absence of protein adsorption. This merit is very large as a container for immunoassay.

Among the immunoanalytical containers, it is necessary to reduce the saturated adsorption amount at a portion that comes into contact with a reagent or a specimen, specifically, the inner surface of the container. Therefore, at least the saturated adsorption amount on the inner surface of the container should be 1 × 10 ⁻¹ pmol / cm ² or less.
In order to reduce the saturated adsorption amount of molecules on the inner surface of the container to 1 × 10 ⁻¹ pmol / cm ² or less, at least the inner surface of the container is molded with a polymer having high hydrophilicity or a polymer having high hydrophobicity, or high hydrophilicity. It is preferable to coat with a polymer having a property or a polymer having a high hydrophobicity. Of these, at least the inner surface of the container is more preferably coated with a highly hydrophilic polymer or a highly hydrophobic polymer, more preferably with a highly hydrophilic polymer, and with a superhydrophilic polymer. Is particularly preferred.

  Examples of the polymer having high hydrophobicity include fluorine resins such as polytetrafluoroethylene (PTFE) or silicon resins. Further, as a means for coating with a hydrophobic polymer, the hydrophobic polymer may be used for coating, but the container may be fluorinated to form a fluorinated polymer on the surface.

  The polymer having high hydrophilicity is not particularly limited as long as it is a polymer having a hydrophilic group such as a carboxyl group or a hydroxyl group, but polymethacrylic acid, (meth) methacrylic acid-alkyl methacrylate copolymer, polyhydroxyalkyl methacrylate ( For example, polyhydroxyethyl methacrylate), hydroxyalkyl methacrylate-alkyl methacrylate copolymer, polyoxyalkylene group-containing methacrylate polymer or a copolymer containing the same, polyvinyl pyrrolidone, ethylene-vinyl alcohol copolymer, (2-methacryloyloxyethyl) Phosphocholine) polymer (MPC) or a copolymer (Biomaterial, Vol. 9, No. 6, 1991) or a phospholipid / polymer complex (Japanese Patent Laid-Open Nos. 5-161491 and 6-6-1) 46 31 No.), and the like. Containers may be formed with these hydrophilic polymers, and these hydrophilic polymers may be coated.

  Moreover, it can also be made low adsorptive by introducing a hydroxyl group and a carboxyl group to the surface of a container once molded with a material suitable for molding such as polystyrene to impart high hydrophilicity. For example, when emphasizing moldability and using materials that tend to cause nonspecific adsorption, such as polystyrene and polypropylene, the introduction of carboxyl groups, carbonyl groups and / or hydroxyl groups by plasma exposure, and transparency are emphasized. If polymethyl methacrylate is used, a surface having low adsorptivity can be realized by surface modification such as introduction of a carboxyl group by surface partial hydrolysis with alkali.

  When reducing the amount of adsorbed molecules by making the inner surface of the container a hydrophilic surface using a hydrophilic polymer, the contact angle of the surface with water is preferably 30 degrees or less (high hydrophilicity), 15 It is more preferable that the temperature be 1 degree or less, and it is even more preferable to be 1 degree or less (super hydrophilicity).

Among the hydrophilic polymers, polyhydroxyalkyl methacrylate, polyoxy C ₂ -C ₄ alkylene group-containing methacrylate polymer or a copolymer containing the same, (2-methacryloyloxyethylphosphocholine) polymer or a copolymer containing the same When a polymer, a phospholipid / polymer complex, or polyvinylpyrrolidone is used, the contact angle with water on the surface of the obtained container becomes superhydrophilic with 1 ° or less, and the saturated adsorption amount of protein is 1 × 10 ⁻³ pmol. / Cm ² or less, which is particularly preferable.

  The shape of the container of the present invention is not particularly limited, such as a conventionally used sample tube, centrifuge tube, multiwell plate, cuvette, etc. The purpose of storing, diluting, reacting, and measuring a sample in one kind of container For this, the shape of a multiwell plate is suitable.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in detail, this invention is not limited to this at all.

(Example 1)
A commercially available 96-well plate made of polypropylene (MS-3396P manufactured by Sumitomo Bakelite) was treated with γ-rays of 70 kGy to produce hydroxyl groups on the surface of the substrate as Example 1. The protein saturated adsorption amount of the obtained plate was 4.6 × 10 ⁻² pmol / cm ² , and the contact angle with water was 27 degrees.

(Example 2)
A commercially available 96-well plate made of polypropylene (MS-3396P made by Sumitomo Bakelite) was fluorine coated on the surface with a commercially available fluorine coating agent (Scotch guard made by Sumitomo 3M). The obtained plate had a saturated protein adsorption of 2.7 × 10 ⁻² pmol / cm ² and a contact angle with water of 126 degrees.

(Comparative Example 1)
A commercially available 96-well polypropylene plate (MS-3396P, manufactured by Sumitomo Bakelite) was used as a comparative example. The protein saturated adsorption amount of this plate was 3.7 pmol / cm ² , and the contact angle with water was 92 degrees.

(Comparison of protein recovery rate as storage container)
In order to compare nonspecific adsorptivity, an enzyme-labeled anti-bovine albumin antibody (manufactured by Cosmo Bio) was used in a concentration series of 0.1 ng / mL, 1 ng / mL, 10 ng / mL, and 100 ng / mL, and each concentration was 24. Each well was dispensed and stored at −80 ° C. for 48 hours, and the protein concentration in the solution after storage was measured using the substrate solution.
The results are as shown in FIG. 1 and confirmed that the protein recovery rate was higher than that of Comparative Example 1 together with the plates of Examples 1 and 2.

(Comparison of reaction efficiency in solution)
In order to evaluate the reaction efficiency in the reaction in the solution, Example 1, Example 2, and Comparative Example 1 were used as reaction containers, and the following examination was performed.
Rat albumin (manufactured by Cosmo Bio) was adjusted to a phosphate buffer solution (Dulbecco PBS pH 7.4) in a concentration series of 10 ng / mL, 1 ng / mL, and 0.1 ng / mL. Dispense 4 rows (32 wells) at 100 μl / well into the plate of Example 1.
Then, a 100 ng / mL phosphate buffer solution (Dulbecco PBS pH 7.4) solution of peroxidase-labeled anti-rat albumin antibody (manufactured by Cosmo Bio) was dispensed to all wells at 100 μl / well.
After reacting at 37 ° C. for 30 minutes, the solution in each well was transferred to a 96-well plate for ELISA in which an anti-rat albumin antibody was immobilized in advance, and then reacted again at 37 ° C. for 30 minutes.

After the reaction, the unreacted labeled anti-rat albumin antibody was washed with a washing solution (Dulbecco PBS pH 7.4 + 0.05% Tween · 20), and then developed using a commercially available color kit for peroxidase (ML-1120T manufactured by Sumitomo Bakelite). Absorbance at 450 nm was measured with a plate reader.
The results are as shown in FIG. 2. In Comparative Example 1, it can be said that the absorbance in the low concentration region is low and the reaction in the solution is inhibited by adsorption. It is understood that linearity is obtained in the absorbance value with respect to the albumin concentration, and the antigen-antibody reaction in the solution is efficiently performed.

(Example 3)
Example 1 was obtained by coating the surface of a commercially available polystyrene tube (Eiken tube RIA No. 3 70-12458) with poly-hydroxyethyl methacrylate (P-3932 made by SIGMA). The protein saturated adsorption amount of the tube was 9.1 × 10 ⁻⁴ pmol / cm ² , and the contact angle with water was 0 degree.

Example 4
Polytetrafluoroethylene was cut, and a tube having the same inner diameter and volume as the tube used in Example 1 was produced as Example 2. The protein saturated adsorption amount of the tube was 7.2 × 10 ⁻³ pmol / cm ² , and the contact angle with water was 126 degrees.

(Comparative Example 2)
A commercially available polystyrene tube (Eiken tube RIA No. 3 70-12458) was used as Comparative Example 2. The protein saturated adsorption amount of the tube was 8.1 pmol / cm ² , and the contact angle with water was 85 degrees.

(Comparison of measurement sensitivity)
In order to evaluate the measurement sensitivity in the reaction in the solution, Examples 3 and 4 and Comparative Example 2 were used as reaction containers, and measurement was performed using an ELISA ball as a reaction carrier.
An ELISA ball (amino group ball manufactured by Sumitomo Bakelite) using a phosphate buffer solution (pH 7.4) of biotin hydrazide (manufactured by Dojindo) previously adjusted in a concentration series of 0.125, 0.250, 0.500 μg / mL. The biotin hydrazide was solid-phased by covalent bonding via glutaraldehyde to prepare an ELISA ball having a three-stage biotin hydrazide solid-phase density.
The portions other than the biotin hydrazide immobilized on the ELISA balls were blocked with skim milk to prevent adsorption.

In each of the three tubes of Examples 3 and 4 and Comparative Example 2, the three-stage biotin hydrazide immobilized density ELISA balls were placed, and 1 μg / mL phosphate buffer (pH 7.) of peroxidase-labeled avidin (manufactured by Cappel). 4) The solution was dispensed at 500 mL / tube and reacted at room temperature for 30 minutes.
After the reaction, the plate is washed with a washing solution (phosphate buffer pH 7.4 + 0.05% Tween · 20), unreacted peroxidase-labeled avidin is washed, and then a commercially available color kit for peroxidase (ML-1120T manufactured by Sumitomo Bakelite) is used. The color was developed, and the absorbance at 450 nm was measured with a plate reader.
The results are as shown in Table 1. In the comparative example, the absorbance changes linearly according to the density of biotin hydrazide introduced on the surface of the ELISA ball. There is no change.
That is, in the examples, peroxidase-labeled avidin reacts only with biotin hydrazide introduced on the ELISA ball surface, and as a result, the absorbance is proportional to the biotin hydrazide density. This is probably because peroxidase-labeled avidin remaining in the tube by adsorption became background and the sensitivity decreased.

(Comparison of protein recovery rate as storage container)
In order to compare nonspecific adsorptivity, an enzyme-labeled anti-bovine albumin antibody (manufactured by Cosmo Bio) was used in a concentration series of 0.1 ng / mL, 1 ng / mL, 10 ng / mL, and 100 ng / mL, and each concentration was 24. Each well was dispensed and stored at −80 ° C. for 48 hours, and the protein concentration in the stored solution was measured using the substrate solution.
The results are shown in Table 2. It was confirmed that the protein recovery rate was higher than that of Comparative Example 2 together with the plates of Examples 3 and 4.

(Example 5)
Dispense 2.5 mL of a 2.0 wt / vol% methanol solution of poly-hydroxyethyl methacrylate (SIGMA P-3932) onto the surface of a commercially available polystyrene tube (Eiken tube RIA No. 3 70-12458), After discharging the solution, the tube was coated with poly-hydroxyethyl methacrylate on the surface by drying for 24 hours at room temperature with the remaining solution turned upside down so as not to accumulate on the bottom surface. The amount of protein saturated adsorption of the obtained tube was 8.7 × 10 ⁻⁴ pmol / cm ² , and the contact angle with water was 0 degree.

(Example 6)
Dispense 2.5 mL of 0.5 wt / vol% ethanol solution of MPC polymer onto the surface of a commercially available polystyrene tube (Eiken tube RIA No.3 70-12458), leave it at room temperature for 10 minutes, and discharge the solution. Then, in a state where the remaining solution was turned over so that it did not accumulate on the bottom surface, the tube was dried overnight at room temperature to produce a tube coated with MPC polymer on the surface. The amount of protein saturated adsorption of the obtained tube was 6.5 × 10 ⁻⁴ pmol / cm ² , and the contact angle with water was 0 degree.

  The MPC polymer was synthesized according to the content of “Papers of Drug Release Polymers from Hydrogel Membranes Having a Phospholipid-like Structure, 46, 591-595 (1989)” ratio of MPC to BMA (butyl methacrylate) = 3 / A copolymer of 7 was prepared and used.

(Comparative Example 3)
A commercially available polystyrene tube (Eiken Tube RIA No. 3 70-12458) was used as it was.

(Comparison of measurement sensitivity)
In order to evaluate the measurement sensitivity in the reaction in the solution, each tube of Example 5, Example 6 and Comparative Example 3 was used as a reaction vessel, and measurement was performed using an ELISA ball (amino group ball manufactured by Sumitomo Bakelite) as a reaction carrier. Carried out.

Use biotin hydrazide (manufactured by Dojindo) adjusted in a concentration series of 0.125, 0.250, and 0.500 μg / mL in a phosphate buffer (pH 7.4) solution, and then add biotin hydrazide to glutaraldehyde in an ELISA ball. Then, it was immobilized by covalent bonding to produce an ELISA ball having a three-stage biotin hydrazide solid phase density.
The portions other than the biotin hydrazide immobilized on the ELISA balls were blocked with skim milk to prevent adsorption.

  Three steps of biotin hydrazide immobilized density ELISA balls were placed in three tubes of Example 5, Example 6 and Comparative Example 3, and 1 μg / mL phosphate buffer (pH 7.) of peroxidase-labeled avidin (manufactured by Cappel). 4) The solution was dispensed at 500 mL / tube and reacted at room temperature for 30 minutes.

  After the reaction, the plate is washed with a washing solution (phosphate buffer pH 7.4 + 0.05% Tween · 20) to wash unreacted peroxidase-labeled avidin, and then a commercially available peroxidase coloring kit (ML-1120T manufactured by Sumitomo Bakelite) is used. The color was developed, and the absorbance at 450 nm was measured with a plate reader.

The results are as shown in Table 3. In the examples, the absorbance also changes linearly according to the density of biotin hydrazide introduced on the ELISA ball surface. There is no change.
That is, in the examples, peroxidase-labeled avidin reacts only with biotin hydrazide introduced on the ELISA ball surface, and as a result, the absorbance is proportional to the biotin hydrazide density. This is probably because the remaining peroxidase-labeled avidin became a background and the sensitivity decreased.

(Comparison of protein recovery rate as storage container)
In order to compare nonspecific adsorptivity, an enzyme-labeled anti-bovine albumin antibody (manufactured by Cosmo Bio) was used in a concentration series of 0.1 ng / mL, 1 ng / mL, 10 ng / mL, and 100 ng / mL. Each well was dispensed and stored at −80 ° C. for 48 hours, and the protein concentration in the stored solution was measured using the substrate solution.
The results are as shown in Table 4. It was confirmed that the protein recovery rate was higher than that of Comparative Example 3 together with the plates of Example 5 and Example 6.

It is a figure which shows the protein concentration after a bovine serum and albumin are preserve | saved at -80 degreeC for 48 hours in the container for immunoassay of this invention. It is a figure which shows reaction efficiency when immunoassay is performed using the container for immunoassay of the present invention.

Claims (10)

A container for immunoassay in which a saturated adsorption amount of molecules used for analysis is 1 × 10 ⁻¹ pmol / cm ² or less.   2. The immunoassay container according to claim 1, wherein at least the inner surface of the container is molded with a highly hydrophilic polymer or a highly hydrophobic polymer, or is coated with a highly hydrophilic polymer or a highly hydrophobic polymer.   2. The immunoassay container according to claim 1, wherein at least the inner surface of the container is molded with a highly hydrophilic polymer or coated with a highly hydrophilic polymer.   The container for immunoassay according to claim 3, wherein a contact angle of the inner surface of the container with water is 30 degrees or less.   The immunoassay container according to claim 3, wherein the contact angle of the inner surface of the container with water is 15 degrees or less.   The container for immunoassay according to claim 3, wherein a contact angle between the inner surface of the container and water is 1 degree or less. Saturated adsorption amount is 1 × 10 ^-3 pmol / cm ² or less immunoassay for enclosure of any one of claims 1 to 6 is of molecules used in the analysis.   The container for immunoassay according to any one of claims 3 to 7, wherein at least an inner surface of the container is coated with a superhydrophilic polymer.   9. The superhydrophilic polymer is selected from polyhydroxyalkyl methacrylate, polyoxy C2-C4 alkylene group-containing methacrylate polymer or a copolymer containing the polymer, polyvinyl pyrrolidone, and a phospholipid / polymer complex. Container for immunoassay.   The container for immunoassay according to claim 8, wherein the superhydrophilic polymer is a (2-methacryloyloxyethyl phosphorylcholine) polymer or a copolymer containing the polymer.