JP6138053B2 - ビタミンdのための放出試薬 - Google Patents
ビタミンdのための放出試薬 Download PDFInfo
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/82—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving vitamins or their receptors
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F14/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen
- C08F14/18—Monomers containing fluorine
- C08F14/26—Tetrafluoroethene
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5002—Partitioning blood components
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
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- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Description
(a)ビタミンD結合タンパク質からのビタミンDの放出を可能にするために、試料に、4〜12個の炭素原子の炭素鎖長を有するペルフルオロアルキル酸、またはその塩を加える工程
(b)任意選択で試料を希釈液で希釈する工程
(c)混合物を固定化結合タンパク質、とりわけ抗ビタミンD抗体と共にインキュベーションにかける工程
(d)試料を、ビタミンDのコンジュゲートおよび競合的に抗ビタミンD抗体と結合する機能性標識と接触させる工程
(e)結合タンパク質に結合した標識化ビタミンD化合物の濃度を測定する工程
を含む方法を提示する。
(a)希釈液/アッセイバッファーを試料に加える工程
(b)抗ビタミンD抗体でコーティングした磁性粒子を加える工程
(c)試料をある一定量の時間インキュベートする工程
(d)ビタミンDのコンジュゲートおよび機能性標識を加える工程
(e)ビタミンDのコンジュゲートおよび抗体に結合した機能性標識の量を測定する工程
を含む。
ビタミンDの測定
アッセイは、自動化プラットフォームを使用して行った。試料15μlに、試料希釈液/アッセイバッファー255μlを加えた。希釈した試料100μlのアリコートを第2のインキュベーションウェルに移した。モノクローナル抗体でコーティングした体積が50μlの磁性粒子を、希釈した試料に加え、37℃で45分間インキュベートした。続いてビオチン化ビタミンDの溶液50μlを加え、37℃で7分間インキュベートした。次いでストレプトアビジン-アクリジニウムエステル溶液50μlを加え、再度37℃で7分間インキュベートした。結合および遊離型ビオチン化ビタミンDの磁気分離後、結合アクリジニウムエステルを定量した。
常磁性粒子 磁性粒子(Invitrogen、M280トシル活性化、2.8μm)を、マウスIgG(5μg/mgの磁性粒子)に対するポリクローナル抗体でコーティングした。粒子を、pH 7.4の0.01M PBS、0.138M NaCl中0.5mg/mlの濃度で16時間の間、ローラー上でコーティングした。最後に、粒子を、0.05Mトリス/0.05%BSA含有0.1%プロクリン-950でブロックした。粒子を、16時間の間37℃で0.4μg/mg粒子の濃度の抗ビタミンDモノクローナル抗体の第2層でコーティングした。
試料15μlに、試料希釈液/アッセイバッファー255μlを加えた。希釈した試料100μlのアリコートを第2のインキュベーションウェルに移した。モノクローナル抗体でコーティングした体積が50μlの磁性粒子を、希釈した試料に加え、37℃で45分間インキュベートした。続いてビオチン化ビタミンDの溶液50μlを加え、37℃で7分間インキュベートした。次いでストレプトアビジン-アクリジニウムエステル溶液50μlを加え、再度37℃で7分間インキュベートした。結合および遊離型ビオチン化ビタミンDの磁気分離後、結合アクリジニウムエステルを定量した。トリガー試薬の添加によって化学発光シグナルが発生した。キュベット中で発生したシグナルは、試料または標準物質中の25(OH)ビタミンDの濃度に反比例する。元の試料中の25(OH)ビタミンDの濃度は、未知試料のシグナルを標準物質の応答と比較することによって計算することができる。
以下の表および図1では、検量線を示している。25(OH)ビタミンD3標準物質は、ビタミンDを含まない血清で調製し、0〜136 ng/mlの範囲であった。
Claims (8)
- 内因性結合タンパク質からビタミンDを放出するための、0.5%ペルフルオロオクタン酸(PFOA)を含むpH8.0の0.1Mトリスバッファーである薬剤を使用した、25-ヒドロキシビタミンDについて血液または血液成分の試料をアッセイするためのイムノアッセイ法。
- (a)試料に、前記薬剤を加えて混合物を得る工程
(b)混合物を抗ビタミンD抗体と共にインキュベーションにかける工程
(c)試料を、ビタミンDのコンジュゲートおよび競合的に抗ビタミンD抗体と結合する機能性標識と接触させる工程
(d)結合タンパク質に結合した標識化ビタミンD化合物の濃度を測定する工程
を含む、25-ヒドロキシビタミンDの存在について血液または血液成分を定性的にin vitroアッセイするための方法である、請求項1に記載の方法。 - 試料がヒト血清または血漿である、請求項2に記載の方法。
- 結合タンパク質が、磁性粒子上にコーティングした形態で提供される、請求項2または3に記載の方法。
- 機能性標識が、放射標識、蛍光標識、発光標識、ビオチン標識、金標識、酵素標識からなる群から選択される、請求項2から4のいずれか一項に記載の方法。
- 濃度を、総25-OHビタミンDに対する標準物質濃度を参照して測定する、請求項2から5のいずれか一項に記載の方法。
- 請求項1から6のいずれか一項に記載の方法を利用する、血液または血液成分中の25-OHビタミンDを測定するためのイムノアッセイ。
- 固相上に固定化された25-OHビタミンDに対して特異的な抗体と、ビタミンDおよび機能性標識のコンジュゲートとを含む、請求項2から6のいずれか一項に記載の方法を使用してイムノアッセイを実施するためのキット。
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