Protein adsorption inhibitor, substrate having coating layer made of protein adsorption inhibitor on surface thereof, magnetic particles, and protein adsorption inhibition method

Abstract

To provide a protein adsorption inhibitor which is free from concerns associated with biologically derived protein adsorption inhibitors, such as biological contamination and lot-to-lot variation, is capable of highly suppressing protein adsorption to a substrate surface, and cannot be easily decomposed by components in the air, such as oxygen and hydrogen.SOLUTION: A protein adsorption inhibitor is provided, containing a compound represented by formula (1) below as an active ingredient. In formula (1), n represents an integer of 5 to 15.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a protein adsorption inhibitor, a substrate having a coating layer composed of this protein adsorption inhibitor on its surface, magnetic particles, and a method for inhibiting protein adsorption using this protein adsorption inhibitor.

Background Art

[0002] For early detection of diseases, measurement methods utilizing immune reactions are widely used in the fields of clinical tests and diagnostic agents. In these immunological measurement methods, while an antibody (protein) causes specific adsorption of the target antigen through an antigen-antibody reaction, it also causes non-specific adsorption to an immune reaction container or a measuring instrument. In addition, serum, cells, and urine used as specimens also contain impurities (proteins) other than the target antigen, and the antibody may also cause non-specific adsorption with these impurities. Such non-specific adsorption of proteins leads to a decrease in measurement accuracy such as an increase in background and the occurrence of false positives.

[0003] Protein adsorption inhibitors are used to suppress such non-specific adsorption of proteins. As typical protein adsorption inhibitors, for example, as disclosed in Patent Document 1, proteins derived from organisms such as bovine serum albumin, gelatin, and skim milk are used. In addition, Patent Document 2 discloses a method of using a copolymer using polyethylene glycol acrylate or polyethylene glycol methacrylate as a monomer as a protein adsorption inhibitor mainly composed of a chemically synthesized product. These methods exhibit effects by physically adsorbing a protein adsorption inhibitor onto the surface of a substrate.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, protein adsorption inhibitors derived from organisms as described in Patent Document 1 have problems such as biological contamination typified by BSE (bovine spongiform encephalopathy) and lot-to-lot variations, and there are further limitations such as storage temperature and expiration date. In addition, in the case of chemically synthesized products as described in Patent Document 2, they have a polyethylene glycol (PEG) skeleton in their structure, and PEG has the characteristic of being easily oxidized by oxygen in the air. There is a problem that the product is liable to deteriorate due to this oxidation of PEG.

[0006] In view of the above problems, the present invention provides a protein adsorption inhibitor that has no concerns caused by protein adsorption inhibitors derived from organisms such as biological contamination and lot-to-lot variations, can highly suppress the adsorption of proteins to the surface of a substrate, and is not easily decomposed by components such as oxygen and water in the air.

Means for Solving the Problems

[0007] As a result of intensive studies in view of the above problems, the present inventors have found that the compound represented by the formula (1) can effectively adsorb to the surface of a substrate such as a reaction vessel or magnetic fine particles, thereby highly suppressing the adsorption of proteins to the surface, and have completed the present invention.

[0008] That is, the present invention is as follows. [1] A protein adsorption inhibitor containing, as an active ingredient, a compound represented by the formula (1). [Chemical formula] [In the formula (1), n is an integer of 5 to 15.] [2] A substrate having, on its surface, a coating layer composed of the protein adsorption inhibitor described in [1] above. [3] Magnetic particles having, on their surface, a coating layer composed of the protein adsorption inhibitor described in [1] above. [4]A method for inhibiting protein adsorption to a substrate, comprising treating the surface of the substrate with the protein adsorption inhibitor according to [1] above to inhibit the adsorption of protein to the surface of the substrate.

Advantages of the Invention

[0009] The protein adsorption inhibitor containing the compound of formula (1) of the present invention can be effectively adsorbed on the surface of substrates such as reaction vessels and magnetic microparticles, thereby highly inhibiting the adsorption of proteins to the surface of the substrate. That is, it exhibits a high ability to inhibit protein adsorption. In addition, there are no concerns such as batch-to-batch differences and biological contamination possessed by protein adsorption inhibitors derived from organisms, and it can safely and stably exhibit the ability to inhibit protein adsorption. Furthermore, the protein adsorption inhibitor of the present invention is difficult to deteriorate and can be made into a protein adsorption inhibitor with a long shelf life.

Embodiments for Carrying Out the Invention

[0010] <Protein Adsorption Inhibitor> Hereinafter, the present invention will be described in more detail. The protein adsorption inhibitor of the present invention is a protein adsorption inhibitor containing a compound of formula (1) as an active ingredient. The protein adsorption inhibitor of the present invention can be used, for example, in immunological assays that utilize enzyme reactions or antigen-antibody reactions, such as those using proteins, polypeptides, steroids, lipids, hormones, etc., and more specifically, various antigens, antibodies, receptors, enzymes, etc. Specifically, the protein adsorption inhibitor of the present invention can be applied to known immunological assays such as radioimmunoassay (RIA), enzyme immunoassay (EIA), fluorescence immunoassay (FIA), latex turbidimetry, and Western blotting. In these known immunological assays, for example, after binding an antibody or antigen to the surface of a substrate, the surface portion of the substrate where the antibody or antigen is not bound can be treated with the protein adsorption inhibitor of the present invention to inhibit the adsorption of non-specific proteins.

[0011] The active ingredient of the protein adsorption inhibitor of the present invention is a compound represented by formula (1).

Chemical Formula

[0012] The compound of formula (1) can be synthesized, for example, by reacting 2-chloro-2-oxo-1,3,2-dioxaphospholane with an n-alcohol in a solvent such as acetonitrile using an amine-based catalyst such as diisopropylamine at -10 to 10 °C for 1 to 5 hours, and then reacting trimethylamine with the filtrate obtained by filtering the reaction solution at room temperature to 80 °C for 10 to 50 hours. As the n-alcohol, an n-alcohol having 6 to 16 carbon atoms is preferred.

[0013] Specific examples of the compound represented by formula (1) include hexyl-2-[trimethylammonio]ethyl phosphate (n = 5 in formula (1)), octyl-2-[trimethylammonio]ethyl phosphate (n = 7 in formula (1)), decyl-2-[trimethylammonio]ethyl phosphate (n = 9 in formula (1)), dodecyl-2-[trimethylammonio]ethyl phosphate (n = 11 in formula (1)), tetradecyl-2-[trimethylammonio]ethyl phosphate (n = 13 in formula (1)), hexadecyl-2-[trimethylammonio]ethyl phosphate (n = 15 in formula (1)), and the like.

[0014] Examples of the compounds that can be contained in the protein adsorption inhibitor other than the compound represented by formula (1) include the following compounds. That is, other reagents and the like commonly used in this field, for example, amino acids and amino acid salts such as glycine, alanine, serine, threonine, glutamic acid, aspartic acid, glutamine, asparagine, lysine, histidine, etc., peptides such as glycylglycine, inorganic salts such as phosphates, borates, sulfates, tris salts, organic acids and organic acid salts such as flavins, acetic acid, citric acid, malic acid, maleic acid, gluconic acid, etc. can be mentioned. The amount of the compound represented by the formula (1) contained in the protein adsorption inhibitor of the present invention may be 100% by mass, but if it is 50% by mass or more, the above effects can be exhibited as an active ingredient.

[0015] The protein adsorption inhibitor of the present invention is preferably dissolved in a solvent or a buffer solution and used as a protein adsorption inhibitor solution. As the solvent, water such as purified water, pure water, ion-exchanged water, or alcohols such as methanol, ethanol, isopropanol can be used. As the buffer solution, any buffer solution that can be used in immunological measurement methods, such as phosphate buffer solution, acetate buffer solution, carbonate buffer solution, citrate buffer solution, tris buffer solution, HEPES buffer solution, physiological saline, etc., can be used without particular limitation. When forming a coating layer by treating the surface of the substrate with the protein adsorption inhibitor solution of the present invention as described later, among the above solvents, water, methanol, ethanol, isopropanol, or a mixture thereof in an arbitrary ratio is preferably used, but a buffer solution may also be used.

[0016] The compound represented by the formula (1) contained in the protein adsorption inhibitor solution is preferably 0.01% by mass or more and 10% by mass or less, more preferably 0.05% by mass or more and 5% by mass or less when n = 5 to 11. When n = 13 to 15, it is preferably 0.001% by mass or more and 5% by mass or less, more preferably 0.01% by mass or more and 0.5% by mass or less. Within these ranges, the protein adsorption inhibitor solution exhibits an effective protein adsorption inhibitory effect.

[0017] Next, a substrate having a coating layer made of a protein adsorption inhibitor on its surface will be described. The substrate in the present invention is an object for which the above-mentioned protein adsorption inhibitor of the present invention is used, and examples thereof include various reaction vessels used in immunoassays, various substances used in immunoassays, etc. Examples of various substances used in immunoassays include carriers such as magnetic particles.

[0018] The material of the substrate such as the magnetic particles used in the present invention is not particularly limited, and examples thereof include metals, ceramics, glass, and resins. More specifically, examples of the substrate material include metal compounds such as iron oxide and iron nitride, and resins such as polystyrene, polypropylene, acrylic resin, polymethyl methacrylate, polyvinylidene fluoride, nylon, and silicone resin. These exemplified substrate materials may be coated with a hydroxyl group, a carboxyl group, a tosyl group, an amino group, avidin, streptavidin, protein A, protein G, albumin, and the like. The metal compound may also be a mixture containing a metal species such as manganese, copper, cobalt, nickel, and zinc in the composition. The shape of the substrate is not particularly limited, but examples include granular, plate-like, block-like, etc. Among these, granular carboxyl-coated iron oxide and polystyrene are preferred.

[0019] As a method for forming a coating layer of the protein adsorption inhibitor of the present invention on the surface of these substrates, for example, the protein adsorption inhibitor of the present invention is dissolved in water, ethanol, isopropanol, or a solvent prepared by mixing these in an arbitrary ratio as described above, and the resulting protein adsorption inhibitor solution is added to a reagent used in various measurements. By using the reagent containing the protein adsorption inhibitor solution thus prepared on the substrate surface, a coating layer can be formed on the substrate surface. When the concentration of the compound represented by the formula (1) in the protein adsorption inhibitor solution for forming the coating layer is n = 5 to 11, it is preferably 0.01% by mass or more and 10% by mass or less, and more preferably 0.05% by mass or more and 5% by mass or less. When n = 13 to 15, it is preferably 0.001% by mass or more and 5% by mass or less, and more preferably 0.01% by mass or more and 0.5% by mass or less.

[0020] Next, the method of using the protein adsorption inhibitor of the present invention will be described. In the present invention, it is possible to provide a method for inhibiting protein adsorption to a substrate, which includes treating the substrate surface with the above-described protein adsorption inhibitor to inhibit the adsorption of protein to the substrate surface. By treating the substrate surface with the protein adsorption inhibitor, a coating layer can be formed on the substrate surface to inhibit the adsorption of protein. As described above, one form of the protein adsorption inhibitor of the present invention is a method of inhibiting the adsorption of protein to the substrate during various measurements by forming a coating layer on the substrate surface by adding the protein adsorption inhibitor solution to a reagent. That is, it is a method of forming a coating layer of the protein adsorption inhibitor on the substrate as one step of various measurements. In addition, the protein adsorption inhibitor of the present invention can be added to and used in any reagent or solution other than the sample to be measured during the measurement. In addition to the method of forming a coating layer of the protein adsorption inhibitor by adding the protein adsorption inhibitor of the present invention to a reagent used in various measurements, there is a method of previously providing a coating layer of the protein adsorption inhibitor of the present invention on the surface of a substrate such as an immunoreaction vessel or a measuring instrument. That is, the compound represented by the formula (1) adsorbs as a coating layer on the surface of a substrate such as an immunoreaction vessel or a measuring instrument, thereby suppressing the adsorption of protein on the surface. In such a method of use, when the concentration of the compound represented by the formula (1) in each reagent and solution is n = 5 to 11, it is preferably 0.01% by mass or more and 10% by mass or less, more preferably 0.05% by mass or more and 5% by mass or less. When n = 13 to 15, it is preferably 0.001% by mass or more and 5% by mass or less, more preferably 0.01% by mass or more and 0.5% by mass or less. However, when adding a protein adsorption inhibitor to a reagent or solution as one step of various measurements, it is performed before adding a protein-containing sample such as serum, labeled antibody, or labeled antigen which is the measurement object.

[0021] Also, as another usage form, a method can be mentioned in which, first, a protein contained in a sample such as an enzyme, a labeled antibody, or a labeled antigen is bound to the surface of a substrate such as the above-described immunoreaction vessel, measuring instrument, or magnetic fine particles, and then the surface of the substrate is treated with the protein adsorption inhibitor of the present invention. For example, when using magnetic fine particles having a carboxyl group coating layer of iron oxide as a substrate, a protein which is a measurement object is physically adsorbed or chemically bonded to the fine particles, washed with an appropriate solvent, and then contacted with the protein adsorption inhibitor solution of the present invention. That is, after adsorbing the measurement object on the fine particle surface, the protein adsorption inhibitor of the present invention is adsorbed in order to suppress the adsorption of protein to the surface portion of the substrate where the object is not adsorbed. Thereby, a substrate having a protein adsorption inhibitory effect can be obtained. As the substrate in such a method of use, substrates of the same types and shapes as the above-described "substrate having a coating layer composed of a protein adsorption inhibitor on the surface" can be exemplified.

Example

[0022] The present invention will be described in more detail with the following examples and comparative examples, but the present invention is not limited thereto. In this example, the compound of (1) shown in each of the following synthesis examples was used as the active ingredient of each protein adsorption inhibitor.

[0023] <Synthesis of the compound represented by formula (1)> (Synthesis Example 1) 17.11 g (0.12 mol) of 2-chloro-2-oxo-1,3,2-dioxaphospholane and 12.2 g (0.12 mol) of 1-hexanol were dissolved in 100 g of acetonitrile (MeCN). 13.37 g (0.13 mol) of diisopropylamine was added as a base, and the mixture was reacted at 0 °C for 2 hours. Then, the reaction solution was filtered and purified. Next, 93.67 g (0.24 mol) of trimethylamine (TMA) was added to the obtained compound (filtrate), and the mixture was reacted at 75 °C for 14 hours. After solvent removal and purification by recrystallization, a white powder of hexyl(2-[trimethylammonio]ethyl)phosphate (n = 5), which is a compound represented by formula (1), was obtained.

[0024] (Synthesis Example 2) Using 1-octanol instead of 1-hexanol and changing the charged amounts so that the molar ratio was the same as in Synthesis Example 1, a white powder of octyl(2-[trimethylammonio]ethyl)phosphate (n = 7 in formula (1)), which is a compound represented by formula (1), was obtained in the same manner as in Synthesis Example 1.

[0025] (Synthesis Example 3) Using 1-decanol instead of 1-hexanol and changing the charged amounts so that the molar ratio was the same as in Synthesis Example 1, a white powder of decyl(2-[trimethylammonio]ethyl)phosphate (n = 9 in formula (1)), which is a compound represented by formula (1), was obtained in the same manner as in Synthesis Example 1.

[0026] (Synthesis Example 4) Using lauryl alcohol instead of 1-hexanol and changing the charged amounts so that the molar ratio was the same as in Synthesis Example 1, a white powder of dodecyl(2-[trimethylammonio]ethyl)phosphate (n = 11 in formula (1)), which is a compound represented by formula (1), was obtained in the same manner as in Synthesis Example 1.

[0027] (Synthesis Example 5) Using 1-tetradecanol instead of 1-hexanol and changing the charged amount so that the molar ratio is the same as in Synthesis Example 1, a white powder of tetradecyl(2-[trimethylammonio]ethyl)phosphate (n = 13 in formula (1)), which is a compound represented by formula (1), was obtained in the same manner as in Synthesis Example 1.

[0028] (Synthesis Example 6) Using 1-hexadecanol instead of 1-hexanol and changing the charged amount so that the molar ratio is the same as in Synthesis Example 1, a white powder of hexadecyl(2-[trimethylammonio]ethyl)phosphate (n = 15 in formula (1)), which is a compound represented by formula (1), was obtained in the same manner as in Synthesis Example 1.

[0029] (Example 1-1) 〈Preparation of Protein Adsorption Inhibitor Solution〉 The compound of Synthesis Example 1 was dissolved in Dulbecco's phosphate Buffered Saline (hereinafter abbreviated as D-PBS, a phosphate buffer solution manufactured by Sigma Aldrich) to a concentration of 0.5% by mass.

[0030] 〈Preparation of Protein Adsorption Inhibitor Antibody Solution〉 A 100-fold diluted Goat Anti-Mouse IgG (H+L) horseradish peroxidase conjugate (an antibody manufactured by Bio-Rad) was prepared and mixed with the protein adsorption inhibitor solution to prepare a protein adsorption inhibitor antibody solution.

[0031] 〈Evaluation of Protein Adsorption Inhibiting Effect〉 Regarding the above protein adsorption inhibitor antibody solution, its protein adsorption inhibiting effect was measured by the following method. Dynabeads TM MyOne TMCarboxylic Acid (manufactured by Thermo Fisher Scientific, hereinafter referred to as magnetic microparticles) was diluted 50-fold with D-PBS to prepare a suspension. The above suspension was dispensed at 100 μL / well into an Eppendorf (trademark) Microplate 96 / V-PP (manufactured by Eppendorf). After the magnetic microparticles were sedimented using a magnet and the supernatant was completely removed, 100 μL / well of D-PBS was dispensed to wash the magnetic microparticles. After the magnetic microparticles were sedimented using a magnet and the supernatant was discarded again, the prepared protein adsorption inhibitor antibody solution was dispensed at 100 μL / well. After dispersing the magnetic microparticles, they were allowed to stand at room temperature for 1 hour. After the magnetic microparticles were sedimented using a magnet and the supernatant was discarded again, a phosphate buffer solution containing 0.05% by mass of Tween 20 (polyoxyethylene sorbitan monolaurate) (hereinafter referred to as PBS-T) was dispensed at 100 μL / well, and the supernatant was completely removed using a magnet. The magnet was removed, 100 μL / well of PBS-T was dispensed, and the total volume of the solution was transferred to an unused well. The supernatant was completely removed using a magnet, the magnet was removed, and a solution prepared by mixing QuantaBlu Substrate Solution / QuantaBlu Stable Peroxidase Solution (both manufactured by Thermo Fisher Scientific) in a ratio of 9 to 1 was dispensed at 100 μL / well and allowed to stand at room temperature for 5 minutes. 100 μL / well of QuantaBlu Stop Solution (manufactured by Thermo Fisher Scientific) was dispensed to stop the reaction. The supernatant was collected at 150 μL / well using a magnet and transferred to a 96F Nontreated Black Microwell SI (manufactured by Thermo Fisher Scientific). Then, fluorescence measurement was performed at an excitation wavelength of 325 nm and a detection wavelength of 420 nm using a microplate reader Spectra Max M3 (manufactured by Molecular Device) to detect the adsorbed protein. A lower fluorescence intensity indicates that the adsorption of the protein is more inhibited.

[0032] The protein adsorption inhibitory effect was evaluated from the relative protein adsorption rate calculated by the following formula using the fluorescence intensity of Example 1-1 and the fluorescence intensity of Comparative Example 1-1 below. That is, it was evaluated by the relative adsorption rate when the protein adsorption rate of the magnetic microparticles in Example 1-1 was set to 100% of the protein adsorption rate to the magnetic microparticles in Comparative Example 1-1. Protein adsorption rate of Example 1-1 = (Fluorescence intensity of Example 1-1 / Fluorescence intensity of Comparative Example 1-1) × 100 Also, when the protein adsorption rate calculated from the above formula was less than 10%, the judgment was "◎", when it was 10% or more and less than 30%, the judgment was "〇", when it was 30% or more and less than 50%, the judgment was "△", and when it was 50% or more, the judgment was "×". The results are shown in Table 1.

[0033] (Example 1-2) The compound of Synthesis Example 2 was used instead of the compound of Synthesis Example 1, and a protein adsorption inhibitor antibody solution was prepared in the same manner as in Example 1-1. Furthermore, the protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1. The results are shown in Table 1.

[0034] (Example 1-3: Examples 1-3-1 to 1-3-3) The compound of Synthesis Example 3 was used instead of the compound of Synthesis Example 1, and a protein adsorption inhibitor antibody solution was prepared in the same manner as in Example 1-1. Furthermore, the protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1. The results are shown in Table 1 as Example 1-3-1. Also, the compound of Synthesis Example 3 was prepared to be 5% by mass and 0.05% by mass in D-PBS, used as a protein adsorption inhibitor antibody solution, and the protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1 except that fluorescence measurement was performed with a microplate reader Infinite 200 PRO M-plex (manufactured by TECAN). The results are shown in Table 2 as Examples 1-3-2 to 1-3-3.

[0035] (Example 1-4: Examples 1-4-1 to 1-4-3) Instead of the compound of Synthesis Example 1, the compound of Synthesis Example 4 was used, and a protein adsorption inhibitor antibody solution was prepared in the same manner as in Example 1-1. Furthermore, the protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1. The results are shown in Table 1 as Example 1-4-1. Also, the compound of Synthesis Example 4 was prepared in D-PBS at 5% by mass and 0.05% by mass, and used as a protein adsorption inhibitor antibody solution. The protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1, except that fluorescence measurement was performed with a microplate reader Infinite 200 PRO M-plex (manufactured by TECAN). The results are shown in Table 2 as Examples 1-4-2 to 1-4-3.

[0036] (Example 1-5: Examples 1-5-1 to 1-5-4) Instead of the compound of Synthesis Example 1, the compound of Synthesis Example 5 was used, and a protein adsorption inhibitor antibody solution was prepared in the same manner as in Example 1-1. Furthermore, the protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1. The results are shown in Table 1 as Example 1-5-1. Also, the compound of Synthesis Example 5 was prepared in D-PBS at 5% by mass, 0.05% by mass, and 0.01% by mass, and used as a protein adsorption inhibitor antibody solution. The protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1, except that fluorescence measurement was performed with a microplate reader Infinite 200 PRO M-plex (manufactured by TECAN). The results are shown in Table 2 as Examples 1-5-2 to 1-5-4.

[0037] (Example 1-6: Examples 1-6-1 to 1-6-4) Instead of the compound of Synthesis Example 1, the compound of Synthesis Example 6 was used, and a protein adsorption inhibitor antibody solution was prepared in the same manner as in Example 1-1. Furthermore, the protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1. The results are shown in Table 1 as Example 1-6-1. Also, the compound of Synthesis Example 6 was prepared in D-PBS at 5% by mass, 0.05% by mass, and 0.01% by mass, and used as a protein adsorption inhibitor antibody solution. The protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1, except that fluorescence measurement was performed with a microplate reader Infinite 200 PRO M-plex (manufactured by TECAN). The results are shown in Table 2 as Examples 1-6-2 to Example 1-6-4.

[0038] (Comparative Example 1-1) The protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1, except that only D-PBS and the antibody were used without using a protein adsorption inhibitor. The results are shown in Table 1.

[0039] (Comparative Example 1-2: Comparative Examples 1-2-1 to 1-2-4) The protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1, except that bovine serum albumin (manufactured by Sigma Aldrich, hereinafter abbreviated as BSA) was used as the protein adsorption inhibitor and a protein adsorption inhibitor solution prepared to have a solution concentration of 0.5% by mass was used. The results are shown in Table 1 as Comparative Example 1-2-1. Also, BSA was prepared to be 5% by mass, 2% by mass, and 0.05% by mass in D-PBS, used as a protein adsorption inhibitor antibody solution, and the protein adsorption inhibitory effect was evaluated in the same manner as in Example 1-1, except that fluorescence measurement was performed with a microplate reader Infinite 200 PRO M-plex (manufactured by TECAN). The results are shown in Table 2 as Comparative Examples 1-2-2 to 1-2-4.

[0040] [Table 1]

[0041] [Table 2]

[0042] In Examples 1-1 to 1-6 using the protein adsorption inhibitor of the present invention containing the compound represented by formula (1) as an active ingredient, a smaller protein adsorption rate was shown compared to the result of Comparative Example 1-1. From this, it was shown that the protein adsorption inhibitor of the present invention containing the compound represented by formula (1) as an active ingredient has high protein adsorption inhibitory performance. Further, the protein adsorption inhibitor of the present invention containing the compound represented by formula (1) as an active ingredient exhibited protein adsorption inhibitory performance equivalent to that of bovine serum albumin (BSA) of biological origin (Comparative Example 1-2), which is excellent in terms of the protein adsorption inhibitory performance commonly used. Furthermore, when n = 5 to 11 in Examples 1-1 to 1-4, a high protein adsorption inhibitory performance was shown when the concentration of the protein adsorption inhibitor was 0.05% by mass or more, whereas when n = 13 to 15 in Examples 1-5 to 1-6, a high protein adsorption inhibitory performance was shown when the concentration of the protein adsorption inhibitor was 0.01% by mass or more. From this, in the case of the compound having a relatively long carbon chain length with n = 13 to 15, excellent protein adsorption inhibitory performance was shown particularly when the concentration of the protein adsorption inhibitor was low. In addition, since the compound represented by formula (1) is not a protein adsorption inhibitor of biological origin, there are no concerns such as lot-to-lot differences and biological contamination. Furthermore, the compound represented by formula (1) does not have a structure that is easily oxidized by oxygen in the air, such as a polyethylene glycol (PEG) skeleton, and can suppress the deterioration of the product.

Claims

**Claim 1** A protein adsorption inhibitor containing, as an active ingredient, a compound represented by formula (1). 【Chemical 1】 [In formula (1), n is an integer of 5 to 15.] **Claim 2** A substrate having, on its surface, a coating layer composed of the protein adsorption inhibitor according to Claim 1. **Claim 3** Magnetic particles having, on their surface, a coating layer composed of the protein adsorption inhibitor according to Claim 1. **Claim 4** A method for inhibiting protein adsorption to a substrate, which comprises treating the surface of the substrate with the protein adsorption inhibitor according to Claim 1 to inhibit the adsorption of protein to the surface of the substrate.

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