JP2018077046A - Sample pretreatment reagent in lyophilized state - Google Patents

Sample pretreatment reagent in lyophilized state Download PDF

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JP2018077046A
JP2018077046A JP2016216861A JP2016216861A JP2018077046A JP 2018077046 A JP2018077046 A JP 2018077046A JP 2016216861 A JP2016216861 A JP 2016216861A JP 2016216861 A JP2016216861 A JP 2016216861A JP 2018077046 A JP2018077046 A JP 2018077046A
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lyophilized
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JP6801381B2 (en
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孝安 宗宮
Takayasu Somiya
孝安 宗宮
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Abstract

PROBLEM TO BE SOLVED: To provide a sample pretreatment reagent in a lyophilized state having good measurement reproducibility for the use in in-vitro diagnostic agents and the like.SOLUTION: A sample pretreatment reagent contains sugar-alcohol (preferably mannitol and the like) having a lyophilized concentration of 90.0 to 180.0 (preferably 100.0 to 170.0) mg/cmand disaccharide (preferably sucrose and the like) having a lyophilized concentration of 90.0 to 180.0 (preferably 100.0 to 170.0) mg/cm.SELECTED DRAWING: Figure 1

Description

本発明は、体外診断薬等に使用される凍結乾燥形態の検体前処理試薬であって、２種以上の糖を含有することにより測定再現性を向上させる方法に関するものである。   The present invention relates to a freeze-dried specimen pretreatment reagent used for in vitro diagnostics and the like, and relates to a method for improving measurement reproducibility by containing two or more sugars.

体外診断薬に使用される検体前処理試薬は液状形態である検体前処理液として、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前処理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前処理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。   Specimen pretreatment reagents used for in-vitro diagnostics are widely used in the field of clinical tests and the like as specimen pretreatment liquids in liquid form. Although the specimen pretreatment liquid in 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 pretreatment solution fluctuates for each use duration and fluctuates from an accurate measurement value for each use duration. It is feared to continue. 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形態の検体前処理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、検体前処理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。   In Patent Document 1, a specimen pretreatment reagent in a lyophilized form for use in an automatic analyzer is reported. However, Patent Document 1 does not describe anything about the composition and manufacturing method of the specimen pretreatment 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.

特許第５８１１２４４号公報Japanese Patent No. 5811244

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形態の検体前処理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. Therefore, an object of the present invention is to provide a specimen pretreatment reagent in a lyophilized form, which 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、凍結乾燥形態の検体前処理試薬に存在する２種以上の糖を選定し、さらに各成分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 selected two or more sugars present in the lyophilized specimen pretreatment reagent and further optimized the concentration of each component. The inventors have found that the measurement reproducibility is good and have completed the present invention.

即ち本発明は以下のとおりである。
（１）凍結乾燥濃度９０．０〜１８０．０ｍｇ／ｃｍ３の糖アルコール、および凍結乾燥濃度９０．０〜１８０．０ｍｇ／ｃｍ３の二糖類を含有することを特徴とする、凍結乾燥状態の検体前処理試薬。
（２）糖アルコールがマンニトールである、（１）に記載の検体前処理試薬。
（３）二糖類がスクロースである、（１）又は（２）に記載の検体前処理試薬。 That is, the present invention is as follows.
(1), characterized in that it contains a lyophilized concentration 90.0~180.0mg / cm 3 sugar alcohol, and lyophilized concentration 90.0~180.0mg / cm 3 of disaccharides, of lyophilized Sample pretreatment reagent.
(2) The specimen pretreatment reagent according to (1), wherein the sugar alcohol is mannitol.
(3) The specimen pretreatment reagent according to (1) or (2), wherein the disaccharide is sucrose.

以下、本発明を詳細に説明する。   Hereinafter, the present invention will be described in detail.

本発明の検体前処理試薬は、検体中の測定対象が他の分子等によって包接されている場合や過剰な妨害成分を含む場合に、検体を前処理して測定対象を測定可能な状態に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前処理液として使用する。   The sample pretreatment reagent of the present invention is a state in which the measurement target can be measured by pre-processing the sample when the measurement target in the sample is included by other molecules or the like, or when the sample contains excessive interference components. Used to do. In use, a dissolution solution is added and dissolved to use as a sample pretreatment solution.

本発明において体外診断薬とは免疫測定法などで行われるものであり、サンドイッチ法や競合法などによって行われるものが含まれる。   In the present invention, the in-vitro diagnostic agent is performed by an immunoassay or the like, and includes those performed by a sandwich method or a competitive method.

本発明の検体前処理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 sample pretreatment reagent of the present invention is used is not particularly limited, and examples thereof include 25-hydroxyvitamin D, vitamin B12, and folic acid.

本発明において用いられる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前処理試薬において、凍結乾燥濃度９０．０〜１８０．０ｍｇ／ｃｍ３含有されるものであり、好ましくは１００．０〜１７０．０ｍｇ／ｃｍ３、更に好ましくは１０５．０〜１６５．０ｍｇ／ｃｍ３である。ここで凍結乾燥濃度とは、［凍結乾燥状態の検体前処理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前処理試薬の見かけ体積］で表わされる値である。なお、凍結乾燥状態の検体前処理試薬は、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。 As the sugar alcohol used in the present invention, mannitol, xylitol, sorbitol, galactitol, ribitol and the like are preferable, and mannitol is particularly preferable. The sugar alcohol is contained in the freeze-dried specimen pretreatment reagent of the present invention in a freeze-dried concentration of 90.0 to 180.0 mg / cm 3 , preferably 100.0 to 170.0 mg / cm 3 , More preferably, it is 105.0-165.0 mg / cm < 3 >. Here, the lyophilized concentration is a value represented by [weight of sugar alcohol contained in lyophilized specimen pretreatment reagent] / [apparent volume of lyophilized specimen pretreatment reagent]. Note that the specimen pretreatment reagent in a lyophilized state has a minute void rather than a dense inside, but the volume when viewed as one solid including the void is defined as an apparent volume here.

一方、本発明に用いられる二糖類としては、例えばスクロース、ラクツロース、ラクトース、マルトース、トレハロース、セロビオース等を使用することができる。その中でもスクロースが好ましい。二糖類は、本発明の凍結乾燥状態の検体前処理試薬において、凍結乾燥濃度９０．０〜１８０．０ｍｇ／ｃｍ３で含有されるものであり、好ましくは１００．０〜１７０．０ｍｇ／ｃｍ３、更に好ましくは１０５．０〜１６５．０ｍｇ／ｃｍ３である。ここで凍結乾燥濃度とは、［凍結乾燥状態の検体前処理試薬に含有される二糖類の重量］／［凍結乾燥状態の検体前処理試薬の見かけ体積］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 disaccharide used in the present invention, for example, sucrose, lactulose, lactose, maltose, trehalose, cellobiose and the like can be used. Of these, sucrose is preferred. The disaccharide is contained in the freeze-dried specimen pretreatment reagent of the present invention at a freeze-dried concentration of 90.0 to 180.0 mg / cm 3 , preferably 100.0 to 170.0 mg / cm 3. More preferably, it is 105.0 to 165.0 mg / cm 3 . Here, the lyophilized concentration is a value represented by [weight of disaccharide contained in lyophilized specimen pretreatment reagent] / [apparent volume of lyophilized specimen pretreatment reagent]. The apparent volume is as described above.

本発明で検体前処理試薬とは、１つの試薬からなるものでもよく、また複数の試薬からなるものでもよい。検体前処理試薬が複数の試薬からなる場合、そのいずれもが前述の凍結乾燥濃度の糖アルコール及び二糖類を含有する凍結乾燥状態のものである。例えば検体前処理試薬として、アルカリ性試薬（前処理剤）と中和剤の組合せを例示することができる。前処理剤としては、例えば水酸化ナトリウム、水酸化カリウム、水酸化カルシウム、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、ホウ酸ナトリウム等を使用することができる。中和剤としては、例えばリン酸二水素カリウム、リン酸水素二カリウム、リン酸二水素ナトリウム、リン酸水素二ナトリウム、リン酸カルシウム等を使用することができる。   In the present invention, the sample pretreatment reagent may be composed of one reagent or may be composed of a plurality of reagents. When the specimen pretreatment reagent is composed of a plurality of reagents, all of them are in a freeze-dried state containing the sugar alcohol and disaccharide having the above-mentioned freeze-dried concentrations. For example, as a sample pretreatment reagent, a combination of an alkaline reagent (pretreatment agent) and a neutralizing agent can be exemplified. As the pretreatment agent, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, sodium hydrogen carbonate, calcium carbonate, sodium borate and the like can be used. As the neutralizing agent, for example, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, calcium phosphate and the like can be used.

本発明では、凍結乾燥時に蛋白質、界面活性剤、緩衝液や塩類を共有させてもよく、それらは特に限定されるものではないが、蛋白質であれば、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、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。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。緩衝液としては、例えばＴｒｉｓ、ＭＯＰＳＯ、ＭＯＰＳやＭＥＳ等を使用することができ、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。なお、凍結乾燥時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。   In the present invention, proteins, surfactants, buffers and salts may be shared at the time of lyophilization, and these are not particularly limited. Examples of proteins include human serum, human serum albumin, and bovine serum. Bovine serum albumin, collagen peptide, skim milk and the like can be used. As the surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, and a nonionic surfactant can be used. For example, Tris, MOPSO, MOPS, MES, and the like can be used as the buffer solution, and sodium chloride, potassium chloride, magnesium chloride, zinc chloride, and the like can be used as the salts. In addition to these, other reagent components and the like can be allowed to coexist as needed during lyophilization.

本発明の凍結乾燥状態の検体前処理試薬は、必要な成分と共に糖アルコール及び二糖類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二糖類の濃度や凍結乾燥条件を適宜設定すればよい。   The lyophilized specimen pretreatment reagent of the present invention can be produced by lyophilizing a solution in which sugar alcohol and disaccharide are present together with necessary components. At this time, the concentration of saccharide alcohol and disaccharide in the solution and the lyophilization conditions may be appropriately set so that the intended lyophilization concentration is obtained.

本発明の凍結乾燥状態の検体前処理試薬は、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前処理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 pretreatment 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 pretreatment reagent of the present invention is used as an in vitro diagnostic agent, it can be measured with high accuracy.

実施例及び比較例で、２穴容器を用いて凍結乾燥ケーキの見かけ体積を測定する方法を示す図である。In an Example and a comparative example, it is a figure which shows the method of measuring the apparent volume of a freeze-dried cake using a 2 hole container.

以下、実施例により本発明をさらに詳細に説明するが、本発明は本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免疫反応試薬２５−ヒドロキシビタミンＤを用い、２ステップサンドイッチ法により各測定を行った。なお、各検体前処理試薬は後述したようにして調製した。   EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited by a present Example. In addition, each measurement is performed by a two-step sandwich method using the fully automated enzyme immunoassay device AIA-CL2400, manufactured by Tosoh Corporation as the immunoassay device, and the immunoreaction reagent 25-hydroxyvitamin D for the device as the immunoassay reagent. It was. Each specimen pretreatment reagent was prepared as described later.

（実施例１，２、比較例１）
前処理剤と中和剤を有する検体前処理試薬を以下のように調製した。即ち、前処理剤として、３００ｍｍｏｌ／Ｌ水酸化ナトリウム水溶液に、表１に記載の濃度となるようマンニトール及びスクロース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。中和剤として、２００ｍｍｏｌ／Ｌリン酸二水素カリウム水溶液に、表１に記載の濃度となるようマンニトール及びスクロースを添加した溶液を調製し、表１に記載の量を、前述の２穴を有する試薬容器の他方の穴に分注した。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 sample pretreatment reagent having a pretreatment agent and a neutralizing agent was prepared as follows. That is, as a pretreatment agent, a solution in which mannitol and sucrose were added to a 300 mmol / L aqueous sodium hydroxide solution to the concentration shown in Table 1 was prepared, and the amount shown in Table 1 was changed to a reagent container having two holes. Dispensing into one of the holes. As a neutralizing agent, a solution in which mannitol and sucrose are added to a 200 mmol / L potassium dihydrogen phosphate aqueous solution so as to have the concentration shown in Table 1 is prepared, and the amount shown in Table 1 has the two holes described above. Dispense into the other hole of the reagent container. This reagent container has two equivalent holes.

Figure 2018077046
この結果、各試薬容器の各穴に存在するマンニトールとスクロースの絶対量は、各試薬容器及び各穴で差がなく、同一である。これらについて凍結乾燥を行い、検体前処理試薬を得た。これを用いて次の測定再現性試験を行った。なお、検体前処理試薬の見かけ体積を以下のようにして測定した。即ち、前述と同様にして前処理剤と中和剤を調製し、但し中和剤は前処理剤とは異なる試薬容器の他方の穴に分注し、凍結乾燥を行った。このようにして得られた前処理剤又は中和剤を有する２穴試薬容器において、図１に示すように、空の１穴に純水を分注し、その水面が他方の穴に存在する前処理剤又は中和剤の凍結乾燥ケーキと同一の高さとなるよう分注・調整した。次に、その穴に分注された純水の重量から体積を求め、前処理剤又は中和剤の凍結乾燥ケーキの見かけ体積とした。なお、図１では左から順に比較例１、実施例１，２に相当する２穴試薬容器中の前処理試薬の凍結乾燥ケーキ及び純水を示す。このようにして測定した結果、凍結乾燥ケーキはそれぞれ表１に記載の見かけ体積を有し、それをもとにそれぞれのマンニトールとスクロースの凍結乾燥濃度を求め、表１に示した。
Figure 2018077046
 As a result, the absolute amount of mannitol and sucrose present in each hole of each reagent container is the same with no difference between each reagent container and each hole. These were freeze-dried to obtain specimen pretreatment reagents. The following measurement reproducibility test was performed using this. The apparent volume of the sample pretreatment reagent was measured as follows. That is, a pretreatment agent and a neutralizing agent were prepared in the same manner as described above, except that the neutralizing agent was dispensed into the other hole of the reagent container different from the pretreatment agent and freeze-dried. In the two-hole reagent container having the pretreatment agent or the neutralizing agent obtained in this way, as shown in FIG. 1, pure water is dispensed into one empty hole, and the water surface exists in the other hole. It was dispensed and adjusted so as to be the same height as the lyophilized cake of the pretreatment agent or neutralizing agent. Next, the volume was determined from the weight of pure water dispensed into the holes, and the volume was obtained as the apparent volume of the pre-treatment agent or neutralizing agent freeze-dried cake. In FIG. 1, the freeze-dried cake and pure water of the pretreatment reagent in the two-hole reagent container corresponding to Comparative Example 1 and Examples 1 and 2 are shown in order from the left. As a result of the measurement, the freeze-dried cakes each had an apparent volume described in Table 1. Based on this, the freeze-dried concentrations of mannitol and sucrose were obtained and shown in Table 1.

（測定再現性試験）
２５−ヒドロキシビタミンＤ濃度１０．２ｎｇ／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前処理試薬（前処理剤及び中和剤）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、検体前処理液を調製した。それを用いて検体を前処理し、２５−ヒドロキシビタミンＤ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。前処理をした後に２５−ヒドロキシビタミンＤ濃度を測定する一連の操作を１０回繰り返して、２５−ヒドロキシビタミンＤ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。表１中、ＶｉｔＤは２５−ヒドロキシビタミンＤを示す。 (Measurement reproducibility test)
Using human serum having a 25-hydroxyvitamin D concentration of 10.2 ng / mL as a specimen, the lyophilized specimen pretreatment reagents (pretreatment and neutralizing agents) prepared in Examples 1 and 2 and Comparative Example 1 were used. 75 μL of a dissolution solution (dispensing water containing sodium azide) was added and dissolved to prepare a sample pretreatment solution. The specimen was pretreated with it and the 25-hydroxyvitamin D concentration was measured. These series of operations were performed with the automatic immunoassay apparatus. A series of operations for measuring the 25-hydroxyvitamin D concentration after the pretreatment was repeated 10 times, and the average value of the measured values of 25-hydroxyvitamin D was determined. Furthermore, measurement reproducibility was calculated based on the measured value. The results are shown in Table 1. In Table 1, VitD indicates 25-hydroxyvitamin D.

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スクロース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、マンニトール凍結乾燥濃度やスクロース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、得られた検体前処理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では溶解液の液量よりも上部の検体前処理試薬が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、ＣＶ２１．４％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、ＣＶ２．６％、３．４％と測定再現性が良く、これはマンニトールとスクロース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前処理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 and the absolute amount of sucrose contained are the same. However, since the apparent volumes of the obtained freeze-dried cakes are different, the mannitol freeze-drying concentration and the sucrose freeze-drying concentration are different. Since it was dissolved in a certain amount of dispensing water, the concentration of the obtained sample pretreatment liquid should be the same, but the easiness of dissolution differs depending on the freeze-dried concentration. The upper specimen pretreatment reagent becomes difficult to dissolve, or even if it is dissolved, the reagent container does not become uniform and a concentration gradient occurs, resulting in a large difference in measurement and a large CV of 21.4%. It is thought that variation occurred. On the other hand, in Examples 1 and 2, the reproducibility of measurement was good at CV 2.6% and 3.4%, which means that mannitol and sucrose were used as specimen pretreatment reagents in a freeze-dried state at appropriate freeze-drying concentrations. It was thought that it was excellent in solubility because it was contained.

Claims (3)

凍結乾燥濃度９０．０〜１８０．０ｍｇ／ｃｍ３の糖アルコール、および凍結乾燥濃度９０．０〜１８０．０ｍｇ／ｃｍ３の二糖類を含有することを特徴とする、凍結乾燥状態の検体前処理試薬。 Sugar alcohols lyophilized concentration 90.0~180.0mg / cm 3, and freeze-dried, characterized in that it contains a concentration 90.0~180.0mg / cm 3 disaccharides, sample pretreatment of lyophilized reagent. 糖アルコールがマンニトールである、請求項１に記載の検体前処理試薬。 The specimen pretreatment reagent according to claim 1, wherein the sugar alcohol is mannitol. 二糖類がスクロースである、請求項１又は２に記載の検体前処理試薬。 The specimen pretreatment reagent according to claim 1 or 2, wherein the disaccharide is sucrose.
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JPH07500417A (en) * 1991-08-23 1995-01-12 アボツト・ラボラトリーズ Unit-of-use reagent composition for specific binding assays
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JP2005060377A (en) * 2003-07-28 2005-03-10 Yamanouchi Pharmaceut Co Ltd Freeze-dried preparation containing interleukin-11
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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

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05500854A (en) * 1989-04-28 1993-02-18 ハイジィーア　サイエンシィズ，インコーポレイテッド Improved immunoassays containing lyophilized reaction reagent mixtures
JPH07500417A (en) * 1991-08-23 1995-01-12 アボツト・ラボラトリーズ Unit-of-use reagent composition for specific binding assays
JPH0920687A (en) * 1995-07-03 1997-01-21 Nippon Telegr & Teleph Corp <Ntt> Thawing solution of freeze-dry blood
JP2005060377A (en) * 2003-07-28 2005-03-10 Yamanouchi Pharmaceut Co Ltd Freeze-dried preparation containing interleukin-11
WO2005040815A1 (en) * 2003-10-28 2005-05-06 Advanced Life Science Institute, Inc. Method of detecting hepatitis c virus
WO2006036848A2 (en) * 2004-09-24 2006-04-06 Cepheid Multiple bead reagent system for protein based assays with optimized matrices
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

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