JP2018013364A - Sample dilution reagent in lyophilized state - Google Patents
Sample dilution reagent in lyophilized state Download PDFInfo
- Publication number
- JP2018013364A JP2018013364A JP2016141944A JP2016141944A JP2018013364A JP 2018013364 A JP2018013364 A JP 2018013364A JP 2016141944 A JP2016141944 A JP 2016141944A JP 2016141944 A JP2016141944 A JP 2016141944A JP 2018013364 A JP2018013364 A JP 2018013364A
- Authority
- JP
- Japan
- Prior art keywords
- reagent
- lyophilized
- concentration
- dilution reagent
- specimen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Sampling And Sample Adjustment (AREA)
Abstract
Description
本発明は、体外診断薬等に使用される凍結乾燥状態の検体希釈試薬であって、糖アルコールおよび蛋白質を含有することにより測定再現性を向上させることに関するものである。 The present invention relates to a lyophilized specimen dilution reagent used for in vitro diagnostics and the like, and relates to improving measurement reproducibility by containing a sugar alcohol and a protein.
体外診断薬等に使用される検体希釈試薬は、液状形態である検体希釈液として、臨床検査等の分野で広く利用されている。この液状形態である検体希釈液はそのまま使用できる点で測定者への負担は軽いものの、体積と重さの点で運送面においては不利である。また通常はバルク品として供給および使用されているので、環境温度や環境湿度の影響を受けやすい。つまり、開封された状態で使用されるので濃縮の影響を避けることができず、使用継続時間毎に検体希釈液中の有効成分濃度が変動し、使用継続時間毎に正確な測定値から変動していくことが危惧される。よってこれらの問題を解決するための方法が提案されている。 Sample dilution reagents used for in-vitro diagnostics and the like are widely used in the field of clinical tests and the like as sample dilution liquids in liquid form. Although the specimen dilution liquid in the liquid form can be used as it is, the burden on the measurer is light, but it is disadvantageous in terms of transportation in terms of volume and weight. Moreover, since it is normally supplied and used as a bulk product, it is easily affected by environmental temperature and environmental humidity. In other words, since it is used in an opened state, the effect of concentration cannot be avoided, and the active ingredient concentration in the sample diluent varies depending on the duration of use, and varies from an accurate measured value for each duration of use. There is concern about going on. Therefore, a method for solving these problems has been proposed.
特許文献１では、自動分析装置で使用する凍結乾燥状態の検体希釈試薬が報告されている。しかしながら特許文献１においては、検体希釈試薬の組成や製法に関しては、何ら記載されていない。凍結乾燥形態の各種試薬においては、賦形剤としての糖や蛋白質などが使用されている。糖や蛋白質などが少ない場合には形状を維持することが困難であり、輸送中に凍結乾燥物が剥離、破砕され容器の壁や蓋に付着することに起因して測定時の有効成分濃度が変動してしまい、正確な測定値から逸脱することが問題となっている。糖や蛋白質などが多い場合には形状を維持することが可能となるが、その成分や濃度が適切でない場合には再溶解した後の溶解性が悪く、その結果、測定再現性が悪くなり測定対象成分を高精度に測定することが妨げられることが問題となっていた。 Patent Document 1 reports a lyophilized specimen dilution reagent used in an automatic analyzer. However, Patent Document 1 does not describe anything about the composition and production method of the sample dilution reagent. In various lyophilized reagents, sugar, protein, or the like is used as an excipient. When there are few sugars or proteins, it is difficult to maintain the shape, and the concentration of active ingredients at the time of measurement is due to the lyophilized material being peeled off during transportation and crushed and adhered to the container wall and lid. It is a problem that it fluctuates and deviates from an accurate measurement value. It is possible to maintain the shape when there are many sugars and proteins, etc., but when the components and concentrations are not appropriate, the solubility after redissolving is poor, resulting in poor measurement reproducibility and measurement. It has been a problem that measurement of target components with high accuracy is hindered.
臨床検査の分野において、試薬の測定時における再現性は種々の試薬で求められている。そこで本発明の目的は、測定再現性が良好な、体外診断薬等に使用される凍結乾燥状態の検体希釈試薬を提供することである。 In the field of clinical examination, reproducibility at the time of reagent measurement is required for various reagents. Accordingly, an object of the present invention is to provide a lyophilized specimen dilution reagent that is used for in vitro diagnostics and the like with good measurement reproducibility.
本発明者らは、前記課題を解決すべく鋭意検討を行なった結果、凍結乾燥状態の検体希釈試薬に存在する糖および蛋白質の濃度を最適化することにより、測定再現性が良好となることを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above problems, the present inventors have found that measurement reproducibility is improved by optimizing the sugar and protein concentrations present in the lyophilized specimen dilution reagent. The headline and the present invention were completed.
即ち本発明は以下のとおりである。
（１）凍結乾燥濃度３０．０〜９０．０ｍｇ／ｃｍ３の糖アルコール、および凍結乾燥濃度３０．０〜１００．０ｍｇ／ｃｍ３の蛋白質を含有することを特徴とする、凍結乾燥状態の検体希釈試薬。
（２）糖アルコールがマンニトールである、（１）に記載の検体希釈試薬。
（３）蛋白質がウシ血清アルブミンである、（１）又は（２）に記載の検体希釈試薬。
That is, the present invention is as follows.
(1), characterized in that it contains a lyophilized concentration 30.0~90.0mg / cm 3 sugar alcohols, and proteins lyophilized concentration 30.0~100.0mg / cm 3, specimens of lyophilized Diluted reagent.
(2) The specimen dilution reagent according to (1), wherein the sugar alcohol is mannitol.
(3) The specimen dilution reagent according to (1) or (2), wherein the protein is bovine serum albumin.
以下、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明の検体希釈試薬は、測定範囲を超える濃度で存在する測定対象や過剰な妨害成分を含む検体を希釈するために使用される。使用にあたって、溶解液を加えて溶解させて検体希釈液として使用する。 The sample dilution reagent of the present invention is used for diluting a measurement target existing at a concentration exceeding the measurement range or a sample containing an excessive interfering component. In use, a dissolution solution is added and dissolved to use as a specimen dilution solution.
本発明の検体希釈試薬が用いられる測定対象としては、特に限定されるものではないが、例えばヒトイムノグロブリン、β２−ミクログロブリン、フェリチン、α−フェトプロテイン、癌胎児性抗原、ＣＡ１９−９、ＳＣＣ抗原、ＣＡ１５−３、ＣＡ１２５、前立腺特異抗原、甲状腺刺激ホルモン、抗甲状腺ペルオキシターゼ抗体、抗サイログロブリン抗体、肝炎ウイルス抗原、ヒト絨毛性ゴナドトロピン、トリヨードサイロニン、サイロキシン、エストラジオール、プロゲステロン、コルチゾール、テストステロン、デヒドロエピアンドロステロンサルフェイト、インスリン、脳性ナトリウム利尿ペプチド、心房性ナトリウム利尿ペプチド、２５−ヒドロキシビタミンＤ、ビタミンＢ１２又は葉酸等があげられる。 The measurement target in which the specimen dilution reagent of the present invention is used is not particularly limited. For example, human immunoglobulin, β2-microglobulin, ferritin, α-fetoprotein, carcinoembryonic antigen, CA19-9, SCC antigen CA15-3, CA125, prostate specific antigen, thyroid stimulating hormone, antithyroid peroxidase antibody, antithyroglobulin antibody, hepatitis virus antigen, human chorionic gonadotropin, triiodothyronine, thyroxine, estradiol, progesterone, cortisol, testosterone, dehydroepi Examples include androsterone sulfate, insulin, brain natriuretic peptide, atrial natriuretic peptide, 25-hydroxyvitamin D, vitamin B12 or folic acid.
本発明において糖アルコールとしてはマンニトール、キシリトール、ソルビトール、ガラクチトール、リビトール等が好ましく、中でもマンニトールが好ましい。糖アルコールは、本発明の凍結乾燥状態の検体希釈試薬において、凍結乾燥濃度３０．０〜９０．０ｍｇ／ｃｍ３含有されるものであり、好ましくは３５．０〜８０．０ｍｇ／ｃｍ３、更に好ましくは３７．５〜７５．０ｍｇ／ｃｍ３である。ここで凍結乾燥濃度とは、［凍結乾燥状態の検体希釈試薬に含有される糖アルコールの重量］／［凍結乾燥状態の検体希釈試薬の見かけ体積］で表わされる値である。なお、凍結乾燥状態の検体希釈試薬は、内部が緻密ではなく微小な空隙を有するが、その空隙を含めて１つの固体として見た場合の体積をここでは見かけ体積とした。 In the present invention, as the sugar alcohol, mannitol, xylitol, sorbitol, galactitol, ribitol and the like are preferable, and mannitol is particularly preferable. In the freeze-dried specimen dilution reagent of the present invention, the sugar alcohol is contained in a freeze-dried concentration of 30.0 to 90.0 mg / cm 3 , preferably 35.0 to 80.0 mg / cm 3 , Preferably it is 37.5-75.0 mg / cm < 3 >. Here, the lyophilized concentration is a value represented by [weight of sugar alcohol contained in lyophilized specimen dilution reagent] / [apparent volume of lyophilized specimen dilution reagent]. The specimen-diluted reagent in the lyophilized state has a minute void inside rather than a fine one, but the volume when viewed as one solid including the void was defined as the apparent volume here.
一方、本発明に用いられる蛋白質としては、例えばヒト血清、ヒト血清アルブミン、ウシ血清、ウシ血清アルブミン（ＢＳＡ）、コラーゲンペプチド、スキムミルク等を使用することができる。その中でもウシ血清アルブミンが好ましい。蛋白質は、本発明の凍結乾燥状態の検体希釈試薬において、凍結乾燥濃度３０．０〜１００．０ｍｇ／ｃｍ３で含有されるものであり、４０．０〜９０．０ｍｇ／ｃｍ３とすることが好ましく、特に４２．２〜８４．４ｍｇ／ｃｍ３とすることが好ましい。ここで凍結乾燥濃度とは、［凍結乾燥状態の検体希釈試薬に含有される蛋白質の重量］／［凍結乾燥状態の検体希釈試薬の見かけ体積］で表わされる値である。なお、見かけ体積とは前述のとおりである。 On the other hand, as the protein used in the present invention, for example, human serum, human serum albumin, bovine serum, bovine serum albumin (BSA), collagen peptide, skim milk and the like can be used. Of these, bovine serum albumin is preferred. Protein in the sample diluted reagent lyophilized state of the present invention are those contained in a lyophilized concentration 30.0~100.0mg / cm 3, be 40.0~90.0mg / cm 3 Especially, it is particularly preferable to set it to 42.2 to 84.4 mg / cm 3 . Here, the lyophilized concentration is a value represented by [weight of protein contained in lyophilized specimen dilution reagent] / [apparent volume of lyophilized specimen dilution reagent]. The apparent volume is as described above.
本発明の凍結乾燥状態の検体希釈試薬には、緩衝液の構成成分が含まれることが好ましい。また界面活性剤や塩類が含まれることも好ましい。それらは特に限定されるものではないが、界面活性剤であればアニオン性界面活性剤、カチオン性界面活性剤、両性界面活性剤、非イオン性界面活性剤を使用することができる。緩衝液の構成成分としては、例えばＴｒｉｓ、ＭＯＰＳＯ、ＭＯＰＳやＭＥＳ等の構成成分をあげることができ、塩類としては、例えば塩化ナトリウム、塩化カリウム、塩化マグネシウム、塩化亜鉛等を使用することができる。凍結乾燥状態の検体希釈試薬にはこれら以外にも、必要に応じて他の試薬成分等を共存させることもできる。 The lyophilized specimen dilution reagent of the present invention preferably contains a component of a buffer solution. It is also preferable that a surfactant and salts are included. Although they are not particularly limited, anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants can be used as long as they are surfactants. Examples of constituents of the buffer include Tris, MOPSO, MOPS, and MES. Examples of salts include sodium chloride, potassium chloride, magnesium chloride, and zinc chloride. In addition to these, the reagent-diluted reagent in a lyophilized state can coexist with other reagent components as necessary.
本発明の凍結乾燥状態の検体希釈試薬は、必要な成分と共に糖アルコール及び蛋白質を共存させた溶液を凍結乾燥することにより、製造することができる。このとき、目的とする凍結乾燥濃度となるよう、溶液中の糖アルコール及び蛋白質の濃度や凍結乾燥条件を適宜設定すればよい。 The lyophilized specimen dilution reagent of the present invention can be produced by lyophilizing a solution in which sugar alcohol and protein coexist with necessary components. At this time, the concentration of the sugar alcohol and protein in the solution and the lyophilization conditions may be set as appropriate so that the intended lyophilization concentration is obtained.
本発明の凍結乾燥状態の検体希釈試薬は、凍結乾燥した際の容器への適度な固着性を有し、また適当な硬さを有する凍結乾燥ケーキとして得られるため、溶解液を加えた際の溶解性に優れたものである。そのため、本発明の凍結乾燥状態の検体希釈試薬を体外診断薬等に用いれば、精度よく測定することができる。 The specimen-diluted reagent in the lyophilized state of the present invention has an appropriate fixing property to a container when lyophilized and is obtained as a lyophilized cake having an appropriate hardness. It has excellent solubility. Therefore, if the lyophilized specimen dilution reagent of the present invention is used as an in vitro diagnostic agent, it can be measured with high accuracy.
以下、実施例により本発明をさらに詳細に説明するが、本発明はこれら実施例により限定されるものではない。なお、免疫測定装置として全自動エンザイムイムノアッセイ装置ＡＩＡ−ＣＬ２４００、東ソー社製を用い、免疫測定用試薬として当該装置用のＡＩＡ−パックＣＬ プロゲステロンを用い、１ステップディレイ競合法により各測定を行った。 EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited by these Examples. In addition, each measurement was performed by a one-step delay competition method using a fully automatic enzyme immunoassay device AIA-CL2400, manufactured by Tosoh Corporation as an immunoassay device, and AIA-pack CL progesterone for the device as an immunoassay reagent.
（実施例１，２、比較例１）
Ｔｒｉｓ緩衝液に、表１に記載の濃度となるよう、ＢＳＡ及びマンニトールを添加した溶液を調製し、表１に記載の量を、２穴を有する試薬容器の一方の穴に分注した。なおこの試薬容器は、同等の２穴を有するものである。
Examples 1 and 2 and Comparative Example 1
A solution in which BSA and mannitol were added to the Tris buffer so as to have the concentration shown in Table 1 was prepared, and the amount shown in Table 1 was dispensed into one hole of a reagent container having two holes. This reagent container has two equivalent holes.
（測定再現性試験）
プロゲステロン濃度３１．２ｎｇ／ｍＬであるヒト血清を検体として、実施例１，２、比較例１にて調製した凍結乾燥状態の検体希釈試薬に溶解液（アジ化ナトリウムを含む分注水）を７５μＬ加えて溶解し、検体希釈液を調製した。それを用いて検体を希釈し、プロゲステロン濃度を測定した。これら一連の操作は前記自動免疫測定装置で行った。検体の希釈倍率は１０倍と設定し、希釈操作は装置上の自動希釈で実施した。希釈をした後にプロゲステロン濃度を測定する一連の操作を１０回繰り返して、プロゲステロン測定値の平均値を求めた。さらにその測定値を基に、測定再現性を算出した。結果を表１に示す。
(Measurement reproducibility test)
Using human serum with a progesterone concentration of 31.2 ng / mL as a specimen, 75 μL of a lysate (distilled water containing sodium azide) was added to the lyophilized specimen dilution reagent prepared in Examples 1 and 2 and Comparative Example 1. The sample diluted solution was prepared. The specimen was diluted with it and the progesterone concentration was measured. These series of operations were performed with the automatic immunoassay apparatus. The dilution ratio of the specimen was set to 10 times, and the dilution operation was performed by automatic dilution on the apparatus. After dilution, a series of operations for measuring the progesterone concentration was repeated 10 times to obtain an average value of the measured progesterone values. Furthermore, measurement reproducibility was calculated based on the measured value. The results are shown in Table 1.
表１から明らかなように、実施例１，２、比較例１は、含有されるマンニトールの絶対量及びＢＳＡの絶対量はそれぞれ同一である。しかしながら、得られた凍結乾燥ケーキの見かけ体積が異なるため、ＢＳＡ凍結乾燥濃度やマンニトール凍結乾燥濃度は異なっている。それを一定量の分注水で溶解したので、得られた検体希釈液の濃度は同一のはずだが、凍結乾燥濃度によって溶解のしやすさが異なり、比較例１では飴状となった部分が固まって溶解しにくくなったり、溶解しても試薬容器内で均一にならず濃度勾配が生じたりして、測定の間差が大きくなり、ＣＶ１２．１％と測定値に大きなばらつきを生じたと考えられる。これに対し、実施例１，２では、ＣＶ４．０％、３．６％と測定再現性が良く、これはＢＳＡとマンニトールとがそれぞれ適切な凍結乾燥濃度で凍結乾燥状態の検体希釈試薬に含有されていたため、溶解性に優れていたと考えられる。 As is clear from Table 1, in Examples 1 and 2 and Comparative Example 1, the absolute amount of mannitol contained and the absolute amount of BSA are the same. However, since the apparent volumes of the obtained freeze-dried cakes are different, the BSA freeze-dry concentration and the mannitol freeze-dry concentration are different. Since it was dissolved in a certain amount of dispensing water, the concentration of the obtained specimen dilution solution should be the same, but the easiness of dissolution differs depending on the freeze-dried concentration, and in Comparative Example 1, the wrinkled part solidified It becomes difficult to dissolve, or even if dissolved, a concentration gradient is generated in the reagent container, resulting in a large difference in measurement and a large variation in measured values of CV12.1%. . On the other hand, in Examples 1 and 2, CV 4.0% and 3.6% have good measurement reproducibility, and this is because BSA and mannitol are contained in lyophilized specimen dilution reagents at appropriate lyophilization concentrations, respectively. Therefore, it is thought that it was excellent in solubility.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016141944A JP6740768B2 (en) | 2016-07-20 | 2016-07-20 | Lyophilized sample dilution reagent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016141944A JP6740768B2 (en) | 2016-07-20 | 2016-07-20 | Lyophilized sample dilution reagent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018013364A true JP2018013364A (en) | 2018-01-25 |
| JP6740768B2 JP6740768B2 (en) | 2020-08-19 |
Family
ID=61020057
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016141944A Active JP6740768B2 (en) | 2016-07-20 | 2016-07-20 | Lyophilized sample dilution reagent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6740768B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116223813A (en) * | 2023-02-23 | 2023-06-06 | 深圳市雷诺华科技实业有限公司 | Kit for determining myocardial troponin I by electrochemiluminescence chromatography and determination method thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01503599A (en) * | 1987-06-18 | 1989-12-07 | クロモジェニックス アクチーボラグ | Determination of active components in protein hydrolysis |
| JPH07507940A (en) * | 1992-04-24 | 1995-09-07 | アバクシス，インコーポレイテッド | cold storage equipment |
| JP2001272394A (en) * | 1991-08-19 | 2001-10-05 | Abaxis Inc | Reagent composition for analytical test |
| JP2008545958A (en) * | 2005-05-20 | 2008-12-18 | ジェネンテック・インコーポレーテッド | Pretreatment of biological samples from subjects with autoimmune disease |
| JP2011527753A (en) * | 2008-07-10 | 2011-11-04 | サムスン エレクトロニクス カンパニー リミテッド | Reagent cartridge, microfluidic device including the cartridge, manufacturing method of the microfluidic device, and biochemical sample analysis method using the microfluidic device |
| JP2012506027A (en) * | 2008-10-14 | 2012-03-08 | サムスン エレクトロニクス カンパニー リミテッド | Centrifugal force-based microfluidic device and sample analysis method using the microfluidic device |
| US20160187257A1 (en) * | 2014-12-30 | 2016-06-30 | Samsung Electronics Co., Ltd. | Microfluidic device and method of detecting sample supplied to the same |
-
2016
- 2016-07-20 JP JP2016141944A patent/JP6740768B2/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01503599A (en) * | 1987-06-18 | 1989-12-07 | クロモジェニックス アクチーボラグ | Determination of active components in protein hydrolysis |
| JP2001272394A (en) * | 1991-08-19 | 2001-10-05 | Abaxis Inc | Reagent composition for analytical test |
| JPH07507940A (en) * | 1992-04-24 | 1995-09-07 | アバクシス，インコーポレイテッド | cold storage equipment |
| JP2008545958A (en) * | 2005-05-20 | 2008-12-18 | ジェネンテック・インコーポレーテッド | Pretreatment of biological samples from subjects with autoimmune disease |
| JP2011527753A (en) * | 2008-07-10 | 2011-11-04 | サムスン エレクトロニクス カンパニー リミテッド | Reagent cartridge, microfluidic device including the cartridge, manufacturing method of the microfluidic device, and biochemical sample analysis method using the microfluidic device |
| JP2012506027A (en) * | 2008-10-14 | 2012-03-08 | サムスン エレクトロニクス カンパニー リミテッド | Centrifugal force-based microfluidic device and sample analysis method using the microfluidic device |
| US20160187257A1 (en) * | 2014-12-30 | 2016-06-30 | Samsung Electronics Co., Ltd. | Microfluidic device and method of detecting sample supplied to the same |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116223813A (en) * | 2023-02-23 | 2023-06-06 | 深圳市雷诺华科技实业有限公司 | Kit for determining myocardial troponin I by electrochemiluminescence chromatography and determination method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6740768B2 (en) | 2020-08-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106124439A (en) | A kind of detection kit of the glycocholic acid eliminating chyle interference | |
| CN105352958B (en) | Total 25-hydroxy-vitamin D detection kit | |
| JP5442179B2 (en) | Method for suppressing sedimentation of fine particles bound with reactive substance and reagent containing the fine particles | |
| US3565987A (en) | Immunochemical determinations of antigens and antibodies | |
| JP5364310B2 (en) | Method for stabilizing microparticles to which reactive substances are bound, and reagent containing the microparticles | |
| JP2016521353A (en) | Method, apparatus and system for sample analysis | |
| JP2018013364A (en) | Sample dilution reagent in lyophilized state | |
| JP2018077171A (en) | Method of detecting allergen in chocolate sample | |
| Abe et al. | Lymphatic involvement in the disappearance of steroidogenic cells from the corpus luteum during luteolysis | |
| CN108088989A (en) | For the universal dilution of multinomial fluorescence immune chromatography product | |
| JP2010101703A (en) | Immunoassay and measuring reagent kit | |
| CN105929176A (en) | Kit for determining heart-type fatty acid binding protein and preparation method thereof | |
| JP4033534B2 (en) | Method for stabilizing human hemoglobin | |
| JP6873995B2 (en) | Hepcidin detection kit | |
| CN107860930A (en) | The immunoturbidimetry detection reagent and method of a kind of cardic fatty acid binding protein | |
| JP6801381B2 (en) | Freeze-dried sample pretreatment reagent | |
| JP2007240163A (en) | Measuring method of protein in sample and measuring reagent | |
| CN106053364A (en) | Kit for measuring insulin and preparation method of kit | |
| US20080261328A1 (en) | Method of preventing precipitation of a reactive substance-bound microparticle, and reagent containing the micro particle | |
| US20120202297A1 (en) | Gender determination method | |
| JP2010002369A (en) | Methods for extracting, inspecting sample component, and inspection kit | |
| JP6520153B2 (en) | Method for producing enzyme-linked small molecule | |
| JP5831723B2 (en) | Test method and drug for pregnancy and pregnancy hypertension syndrome by autotaxin measurement | |
| JP2004170127A (en) | Blood corpuscle reagent for antibody test | |
| EP3690441A1 (en) | Method for reducing measurement error in latex immunoagglutination assay |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190611 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200317 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200313 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200623 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200706 |
|
| R151 | Written notification of patent or utility model registration |
Ref document number: 6740768 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R151 |