JP5844195B2 - 磁性シリカ粒子並びにこれを用いた免疫測定法及び免疫測定用試薬 - Google Patents
磁性シリカ粒子並びにこれを用いた免疫測定法及び免疫測定用試薬 Download PDFInfo
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- JP5844195B2 JP5844195B2 JP2012075359A JP2012075359A JP5844195B2 JP 5844195 B2 JP5844195 B2 JP 5844195B2 JP 2012075359 A JP2012075359 A JP 2012075359A JP 2012075359 A JP2012075359 A JP 2012075359A JP 5844195 B2 JP5844195 B2 JP 5844195B2
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- magnetic silica
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- JXUKBNICSRJFAP-UHFFFAOYSA-N triethoxy-[3-(oxiran-2-ylmethoxy)propyl]silane Chemical compound CCO[Si](OCC)(OCC)CCCOCC1CO1 JXUKBNICSRJFAP-UHFFFAOYSA-N 0.000 description 1
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- BPSIOYPQMFLKFR-UHFFFAOYSA-N trimethoxy-[3-(oxiran-2-ylmethoxy)propyl]silane Chemical compound CO[Si](OC)(OC)CCCOCC1CO1 BPSIOYPQMFLKFR-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- SJEYEFOHSMBQIX-UHFFFAOYSA-N undecane-1-sulfonic acid Chemical compound CCCCCCCCCCCS(O)(=O)=O SJEYEFOHSMBQIX-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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- Soft Magnetic Materials (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
上記及び以下において、(アルキル)アルコキシシランとは、アルキルアルコキシシラン又はアルコキシシランを意味する。
炭素数2〜30の脂肪族ポリカルボン酸(シュウ酸、マロン酸、コハク酸、グルタル酸、アジピン酸、ピメリン酸、スベリン酸、アゼライン酸、セバシン酸、プロパン−1,2,3−トリカルボン酸、クエン酸及びドデカン二酸等の飽和ポリカルボン酸並びにマレイン酸、フマール酸及びイタコン酸等の不飽和ポリカルボン酸等)、炭素数8〜30の芳香族ポリカルボン酸(フタル酸、イソフタル酸、テレフタル酸、トリメリット酸及びピロメリット酸等)及び炭素数5〜30の脂環式ポリカルボン酸(シクロブテン−1,2−ジカルボン酸、シクロペンテン−1,2−ジカルボン酸、フラン−2,3−ジカルボン酸、ビシクロ[2,2,1]ヘプタ−2−エン−2,3−ジカルボン酸及びビシクロ[2,2,1]ヘプタ−2,5−ジエン−2,3−ジカルボン酸等)等。
炭素数1〜30の脂肪族ポリスルホン酸(メチオン酸、1,1−エタンジスルホン酸、1,2−エタンジスルホン酸、1,1−プロパンジスルホン酸、1,3−プロパンジスルホン酸及びポリビニルスルホン酸等)、炭素数6〜30の芳香族ポリスルホン酸(m−ベンゼンジスルホン酸、1,4−ナフタレンスルホン酸、1,5−ナフタレンジスルホン酸、1,6−ナフタレンジスルホン酸、2,6−ナフタレンジスルホン酸、2,7−ナフタレンジスルホン酸及びスルホン化ポリスチレン等)、ビス(フルオロスルホニル)イミド及び炭素数2〜10のビス(パーフルオロアルカンスルホニル)イミド[ビス(トリフルオロメタンスルホニル)イミド、ビス(ペンタフルオロエタンスルホニル)イミド、ビス(ノナフルオロブタンスルホニル)イミド、ペンタフルオロエタンスルホニルトリフルオロメタンスルホニルイミド、トリフルオロメタンスルホニルヘプタフルオロプロパンスルホニルイミド、ノナフルオロブタンスルホニルトリフルオロメタンスルホニルイミド等]等。
炭素数2〜30のスルホカルボン酸(スルホ酢酸及びスルホコハク酸等)及び炭素数7〜30のスルホ芳香族モノ又はポリカルボン酸(o−、m−又はp−スルホ安息香酸、2,4−ジスルホ安息香酸、3−スルホフタル酸、3,5−ジスルホフタル酸、4−スルホイソフタル酸、2−スルホテレフタル酸、2−メチル−4−スルホ安息香酸、2−メチル−3,5−ジスルホ安息香酸、4−プロピル−3−スルホ安息香酸、4−イソプロピル−3−スルホ安息香酸、2,4,6−トリメチル−3−スルホ安息香酸、2−メチル−5−スルホテレフタル酸、5−メチル−4−スルホイソフタル酸、5−スルホサリチル酸及び3−オキシ−4−スルホ安息香酸等)等。
炭素数1〜30の脂肪族飽和モノカルボン酸(ギ酸、酢酸、プロピオン酸、酪酸、イソ酪酸、吉草酸、カプロン酸、エナント酸、カプリル酸、ベラルゴン酸、ラウリル酸、ミリスチン酸、ステアリン酸及びベヘニン酸等)、炭素数3〜30の脂肪族不飽和モノカルボン酸(アクリル酸、メタクリル酸、オレイン酸、ステアリン酸等)、炭素数3〜30のヒドロキシ脂肪族モノカルボン酸(グリコール酸、乳酸及び酒石酸等)、炭素数4〜30の脂環式モノカルボン酸(シクロプロパンカルボン酸、シクロペンタンカルボン酸及びシクロヘキサンカルボン酸等)、炭素数7〜30の芳香族モノカルボン酸(安息香酸、ケイ皮酸及びナフトエ酸等)、炭素数7〜20のヒドロキシ芳香族モノカルボン酸(サリチル酸及びマンデル酸等)及び炭素数2〜20のパーフルオロカルボン酸(トリフルオロ酢酸、ウンデカフルオロヘキサン酸、トリデカフルオロヘプタン酸、パーフルオロオクタン酸、ペンタデカフルオロオクタン酸、ペプタデカフルオロノナン酸及びノナデカフルオロデカン酸等)等。
炭素数1〜30脂肪族モノスルホン酸(メタンスルホン酸、エタンスルホン酸、プロパンスルホン酸、ブタンスルホン酸、ヘキサンスルホン酸、デカンスルホン酸、ウンデカンスルホン酸及びドデカンスルホン酸等)、炭素数6〜30芳香族モノスルホン酸(ベンゼンスルホン酸、p−トルエンスルホン酸、o−トルエンスルホン酸、m−トルエンスルホン酸、4−ドデシルベンゼンスルホン酸、4−オクチルベンゼンスルホン酸及びナフタレンスルホン酸等)及び炭素数1〜20のパーフルオロアルカンスルホン酸(トリフルオロメタンスルホン酸等)等。
R1 (4-n)Si(OR2)n (1)
一般式(1)中、R1及びR2は、アミノ基、カルボキシル基、水酸基、メルカプト基又はグリシジルオキシ基で置換されていてもよい炭素数1〜10の1価の炭化水素基を表す。
(アルキル)アルコキシシランは、1種類を単独で用いても2種以上を併用してもよい。
加水分解用触媒の使用量は、(アルキル)アルコキシシランの重量に対して、0.01〜100重量%、特に0.2〜50重量%が好ましい。
<一部修正しました>
アルギニン又はアルギニン誘導体の水溶液は、1種類を単独で用いても2種以上を併用してもよい。
また、B/F分離工程は標識複合体の形成後には必須の工程であるが、磁性シリカ粒子表面に測定対象物質結合物質と測定対象物質との複合体を形成させた後においても実施することができる。
これらの内、感度等の観点から、酵素、蛍光性物質が好ましく、更に好ましいのはアルカリホスファターゼ、ペルオキシダーゼ及びグルコースオキシダーゼであり、特に好ましいのはペルオキシダーゼである。
磁性シリカ粒子の量は、特に限定されず、用いられる測定対象物質結合物質又は測定対象物質の類似物質の種類、測定対象物質の種類等により適宜選択できる。
本発明における免疫測定用試薬は、本発明における磁性シリカ粒子が緩衝液に分散された形態であることが好ましい。
これらの内、ルミノール、イソルミノール、N−アミノヘキシル−N−エチルイソルミノール(AHEI)、N−アミノブチル−N−エチルイソルミノール(ABEI)及びこれらの金属塩(アルカリ金属塩等)が好ましく、更に好ましいのはルミノール及びその金属塩、特に好ましいのはルミノールのナトリウム塩である。
これらの内、保存安定性等の観点から、過酸化水素水溶液、過ホウ酸ナトリウム水溶液及び過ホウ酸カリウム水溶液が好ましく、更に好ましいのは過酸化水素水溶液である。
磁性シリカ粒子の製造:
反応容器に塩化鉄(III)6水和物2.7部、塩化鉄(II)4水和物1.0部及び水375部を仕込んで溶解させて50℃に昇温し、攪拌下温度を50〜55℃の保持しながら、25重量%アンモニア水3.8部と水100部を混合した溶液を1時間かけて滴下し、滴下後1時間攪拌し、80℃に昇温後、オレイン酸10.5部加え、2時間攪拌を継続した。室温に冷却後、デカンテーションにより固液分離して得られたオレイン酸が吸着したマグネタイト粒子を水50部で洗浄する操作を4回行った。得られたオレイン酸が吸着したマグネタイト粒子を容器に仕込み、デカン5.7部及びテトラエトキシシラン2.2部を加えて混合し、分散液(A)を調製した。
反応容器に25重量%アンモニア水溶液39.0部、イソプロパノール55.4部、ソルビタンモノオレエート2.9部(三洋化成工業株式会社製「イオネットS−80」)及びポリオキシエチレン(付加モル数20モル)アルキルエーテル(三洋化成工業株式会社製「エマルミン200」)2.0部を加えてヒストコロンNS−56S(マイクロテック・ニチオン社製)を用いて混合し、50℃に昇温後、ヒストコロンの回転数6,000rpmで攪拌しながら、上記分散液(A)を1時間かけて滴下後、50℃で1時間反応させた。反応後、2,000rpmで5分間遠心分離して微粒子の存在する上清を除いた。得られた固相に水50部を加えて粒子を分散させて1,000rpmで10分間遠心分離後、微粒子の存在する上清を除く操作を10回行った。続いて、得られた固相に水50部を加えて粒子を分散させて500rpmで5分間遠心分離することにより、大きな粒子径の粒子を沈降させて目的とする粒子径を有する粒子を含有する上清(1)を回収した。残った固相に水50部を加えて500rpmで5分間遠心分離後、上清(2)を回収する操作を2回行い、固相中に存在する目的とする粒子径を有する粒子を回収した。次に、上清(1)及び(2)について、磁石を用いて粒子を集磁し、集磁された粒子を80℃で8時間乾燥させて磁性シリカ粒子を得た。
1重量%γ−アミノプロピルトリエトキシシラン含有アセトン溶液40mLの入った蓋付きポリエチレン瓶に製造した磁性シリカ粒子40mgを加え、25℃で1時間反応させ、ネオジウム磁石で磁性シリカ粒子を集磁後、液をアスピレーターで吸引除去した。次いで脱イオン水40mLを加えて蓋をし、ポリスチレン瓶をゆっくりと2回倒置攪拌した後、ネオジウム磁石で磁性シリカ粒子を集磁後、液をアスピレーターで吸引除去して磁性シリカ粒子を洗浄した。この洗浄操作を5回行った。次いで、この洗浄後の磁性シリカ粒子を2重量%グルタルアルデヒド含有水溶液40mLの入った蓋付きポリエチレン瓶に加え、25℃で1時間反応させた。そして、脱イオン水40mLを加えて蓋をし、ポリスチレン瓶をゆっくりと2回倒置攪拌したのち、ネオジウム磁石で磁性シリカ粒子を集磁後、液をアスピレーターで吸引除去して磁性シリカ粒子を洗浄した。この洗浄操作を10回行った。更にこの洗浄後の磁性シリカ粒子を抗PSAモノクローナル抗体(ダコジャパン社製)10μg/mLの濃度で含む0.02Mリン酸緩衝液(pH8.7)120mLの入った蓋付きポリエチレン瓶に加え、25℃で1時間反応させた。反応後、ネオジウム磁石で磁性シリカ粒子を集磁後、抗PSAモノクローナル抗体含有リン酸緩衝液を除去した。次いで、磁性シリカ粒子を1重量%のカゼイン含有の0.02Mリン酸緩衝液(pH7.0)40mLの入った蓋付きポリエチレン瓶に加え、25℃で12時間浸漬させたのち、ネオジウム磁石でシリカ粒子を集磁後、1重量%のカゼイン含有のリン酸緩衝液を除去した。これにアルギニン一塩酸塩[和光純薬工業(株)製]0.5M含有の0.02Mリン酸緩衝液(pH7.0)40mLを加え、25℃で12時間浸漬した。浸漬後、ネオジウム磁石で磁性シリカ粒子を集磁後、アルギニン一塩酸塩含有リン酸緩衝液を除去した。更に、1重量%のカゼイン含有の0.02Mリン酸緩衝液(pH7.0)で、アルギニン又はアルギニン誘導体を固定化した抗PSA抗体結合磁性シリカ粒子濃度として1.0mg/mLの濃度に希釈し、磁性シリカ粒子を含有する試薬を調製し、冷蔵(2〜10℃)で保存した。
抗PSAモノクローナル抗体(ダコジャパン社製)、西洋ワサビ由来POD(東洋紡製)を用い、文献(エス・ヨシタケ、エム・イマガワ、イー・イシカワ、エトール;ジェイ.バイオケム,Vol.92,1982,1413−1424)に記載の方法でPOD標識抗PSA抗体を調製した。これを1重量%の牛血清アルブミン含有の0.02Mリン酸緩衝液(pH7.0)で、POD標識抗PSA抗体濃度として100nMの濃度に希釈し、標識試薬を調製し、冷蔵(2〜10℃)で保存した。
ルミノールのナトリウム塩[シグマ アルドリッチ ジャパン(株)製]0.7g及び4−(シアノメチルチオ)フェノール0.1gを1,000mLメスフラスコに仕込んだ。3−[4−(2−ヒドロキシエチル)−1−ピペラジニル]プロパンスルホン酸/水酸化ナトリウム緩衝液(10mM、pH8.6)を溶液の容量が1,000mLになるように仕込み、25℃で均一混合して化学発光試薬第1液を調製した。測定に用いるまで冷蔵(2〜10℃)保存した。
1,000mL及び過酸化水素[和光純薬工業(株)製、試薬特級、濃度30重量%]6.6gを1,000mLメスフラスコに仕込んだ。脱イオン水を溶液の容量が1,000mLになるように仕込み、25℃で均一混合して化学発光試薬第2液を調製した。測定に用いるまで冷蔵(2〜10℃)保存した。
乳化の際のヒストコロンの回転数を6,000rpmから7,500rpmに変更した以外は、実施例1と同様にして免疫測定試薬(S2)を得た。
マグネタイト粒子作製時における25重量%アンモニア水3.8部と混合する水の量を100部から33.8部、テトラエトキシシランの仕込量を2.2部から0.5部に変更した以外は、実施例1と同様にして免疫測定試薬(S3)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをアルギニン[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S4)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをホモアルギニン塩酸塩[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S5)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをアセチルアルギニン[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S6)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをヒドロキシアルギニン酢酸塩[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S7)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをアルギニンメチルエステル二塩酸塩(東京化成工業株式会社製)0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S8)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをアルギニンエチルエステル二塩酸塩[シグマ アルドリッチ ジャパン(株)製]に変更した以外は、実施例1と同様にして免疫測定試薬(S9)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをアルギニンニトロアニリド二塩酸塩[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S10)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをポリアルギニン塩酸塩[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S11)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをメチルアルギニン酢酸塩[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S12)を得た。
磁性シリカ粒子を含有する試薬の作製におけるアルギニン一塩酸塩0.5Mをアグマチン硫酸塩[シグマ アルドリッチ ジャパン(株)製]0.5Mに変更した以外は、実施例1と同様にして免疫測定試薬(S13)を得た。
500rpmで5分間遠心分離することから、300rpmで3分間遠心分離することに変更した以外は、実施例1と同様にして免疫測定試薬(H1)を得た。
テトラエトキシシランの仕込量を0.5部から8.0部に代え、乳化の際のヒストコロンの回転数を6,000rpmから7,500rpmに変更した以外は、実施例3と同様にして免疫測定試薬(H2)を得た。
100部の硫酸第一鉄を1,000部の水に溶解し、攪拌下、水500部に水酸化ナトリウム28.8部を溶解した水溶液を1時間かけて滴下後、攪拌しながら、85℃まで昇温して空気を懸濁液に吹き込み8時間酸化し、遠心分離することにより得られたマグネタイト粒子2.2部をデカン5.7部及びテトラエトキシシラン2.2部と混合して分散液(B)を得た。分散液(A)を分散液(B)に代える以外は、実施例2と同様にして免疫測定試薬(H3)を得た。
アルギニン一塩酸塩500mM含有の0.02Mリン酸緩衝液(pH7.0)を生理食塩水に変更した以外は、実施例1と同様にして免疫測定試薬(H4)を得た。
磁性シリカ粒子を含有する試薬0.025mLとウマ血清で調製したPSA濃度が0.01ng/mLの標準PSA液0.025mLを試験管に入れて混合し、試験管中で37℃3分間反応させ、アルギニン又はアルギニン誘導体を固定化した抗PSA抗体結合磁性シリカ粒子/PSA複合体を形成させた。反応後、試験管の外側からネオジウム磁石で磁性シリカ粒子を10秒間集め、試験管中の液をアスピレーターで除き、ネオジウム磁石を側面から十分に離し、生理食塩水0.5mLを加えて磁性シリカ粒子を分散させて集磁後、アスピレーターで液を除く洗浄操作を3回行った。
最後に、化学発光試薬第1液0.07mLと化学発光試薬第2液0.07mLとを同時に加え、37℃で43秒間発光反応させ、化学発光試薬を添加後43〜45秒の平均発光量をルミノメーター[ベルトールドジャパン社製「Lumat LB9507」]で測定した。尚、PSA濃度が0.1ng/mLの標準PSA液の代わりにPSA濃度が0ng/mLの標準PSA液を使用して上記と同様の操作を行いバックグラウンドとして用いた。
○:10,000cps未満
△:10,000cps以上かつ25,000cps未満
×:25,000cps以上
感度については、PSA濃度が0ng/mLと0.01ng/mLの標準溶液を用いた免疫測定を行った場合の発光量の差から以下の基準で判定した。
○:2,500cps以上
△:1,000cps以上かつ2,500cps未満
×:1,000cps未満
任意の200個の超常磁性金属酸化物について、走査型電子顕微鏡で観察して粒子径を測定し、その平均値を平均粒子径とした。
<磁性シリカ粒子の平均粒子径の測定方法>
任意の200個の磁性シリカ粒子について、走査型電子顕微鏡で観察して粒子径を測定し、その平均値を平均粒子径とした。
<磁性シリカ粒子中の超常磁性金属酸化物の含有量の測定方法>
任意の20個の磁性シリカ粒子について、走査型電子顕微鏡で観察し、エネルギー分散型X線分光装置により超常磁性金属酸化物の含有量を測定してその平均値を含有量とした。
1.0mgの磁性シリカ粒子を2mLのイオン交換水に分散させ、口内径×胴径×全高=φ10.3mm×φ12.0mm×35mmのガラス容器に入れ、1cm×1cm×1cmのネオジウム磁石を側面につけ、初期吸光度が20%となるまでの時間を測定し、以下の基準で判定した。
○:15秒未満
△:15秒以上かつ30秒未満
×:30秒以上
1.0mgの磁性粒子シリカ粒子を2mLのイオン交換水に分散させ、口内径×胴径×全高=φ10.3mm×φ12.0mm×35mmのガラス容器に入れ、1cm×1cm×1cmのネオジウム磁石を側面につけて、磁性シリカ粒子を完全に集磁し、上清を除去し、ネオジウム磁石を側面から十分に離し、2mLのイオン交換水を磁性シリカ粒子に噴きつけながら加え、3回のピペッティングにより混合した後、10秒以内に顕微鏡で観察し、視野内の全粒子数に対する凝集した粒子数の割合を算出して以下の基準で再分散性判定した。
○:凝集粒子が5%未満
△:凝集粒子が5%以上かつ20%未満
×:凝集粒子が20%以上
3回のピペッティングによる混合後、顕微鏡で観察するまでの時間を10秒以内から5分に代える以外は上記再分散性の評価方法と同様にして、視野内の全粒子数に対する凝集した粒子数の割合を算出して以下の基準で判定した。
○:凝集粒子が5%未満
△:凝集粒子が5%以上かつ20%未満
×:凝集粒子が20%以上
Claims (8)
- 平均粒子径が1〜15nmの超常磁性金属酸化物を60〜95重量%含有する磁性シリカ粒子であって、該磁性シリカ粒子表面をTi酸化物で被覆されていない磁性シリカ粒子の表面に、測定対象物質、測定対象物質の類似物質、又は測定対象物質と特異的に結合する物質を固定化し、更にアルギニン、アルギニンの塩、又はホモアルギニン、アセチルアルギニン、ヒドロキシアルギニン、アルギニンメチルエステル、アルギニンエチルエステル、アルギニンニトロアニリド、ポリアルギニン、メチルアルギニン、アグマチン及びこれらの塩からなる群から選ばれる少なくとも1種を固定化させてなることを特徴とする磁性シリカ粒子。
- 測定対象物質、測定対象物質の類似物質、又は測定対象物質と特異的に結合する物質が固定化される前の前記磁性シリカ粒子の表面にグルタルアルデヒド、アルブミン、カルボジイミド、ストレプトアビジン、ビオチン及び官能基を有するアルキルアルコキシシランからなる群から選ばれる少なくとも1種の有機化合物を結合させてなる請求項1記載の磁性シリカ粒子。
- 磁性シリカ粒子の平均粒子径が1〜5μmである請求項1又は2記載の磁性シリカ粒子。
- 超常磁性金属酸化物が酸化鉄である請求項請求項1〜3のいずれか記載の磁性シリカ粒子。
- 酸化鉄がマグネタイト、γ−ヘマタイト、マグネタイト−α−ヘマタイト中間酸化鉄及びγ−ヘマタイト−α−ヘマタイト中間酸化鉄からなる群から選ばれる少なくとも1種の酸化鉄である請求項4記載の磁性シリカ粒子。
- 測定対象物質と特異的に結合する物質が、測定対象物質若しくは測定対象物質の類似物質に対する抗体、測定対象物質若しくは測定対象物質の類似物質が結合する抗原、又は測定対象物質若しくは測定対象物質の類似物質に結合するタンパク質である請求項1〜5のいずれか記載の磁性シリカ粒子。
- 請求項1〜6のいずれか記載の磁性シリカ粒子を用いることを特徴とする免疫測定法。
- 請求項1〜6のいずれか記載の磁性シリカ粒子を用いることを特徴とする免疫測定用試薬。
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