JP5050058B2 - 血液型の判定 - Google Patents
血液型の判定 Download PDFInfo
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Description
新生児溶血性疾患(HDN、または胎児赤芽球症とも呼ばれる)
抗D抗体による新生児溶血性疾患(Rh血液型不適合とも呼ばれる)
ABO式血液型不適合による新生児溶血性疾患
抗K(ケル)による新生児溶血性疾患
抗C抗体による新生児溶血性疾患
他の血液型不適合(Rhc、Rhe、RhE、Kid、Duffy、MN、Pその他)
同種溶血性輸血反応
自己免疫性溶血性疾患の例として:
温式抗体自己免疫性溶血性貧血
特発性溶血性貧血
全身性エリテマトーデス
エバンス症候群(抗血小板抗体および溶血抗体)
寒冷抗体自己免疫性溶血性貧血
特発性寒冷血球凝集素症
感染性単核球症
発作性寒冷血色素尿症(希)
薬剤惹起性免疫性溶血性貧血
−メチルドーパ型
−ペニシリン型(高用量)
様々な前記特徴的抗体/補体因子と特異的に結合する多数の結合剤を、基板上のあらかじめ定めた位置に個別に固定したマイクロアレイを提供し、
前記マイクロアレイに、被験者から採取した血液サンプルを接触させ、
前記結合剤を固定した1つ以上の領域から、非結合の赤血球を実質的に全て除去し、
前記マイクロアレイと結合した赤血球(前記特徴的抗体を介して)の存在を検出し、
これにより、特徴的抗体/補体因子が被験者の赤血球と結合したかどうかを判断する。
Milliore社(U.K.)製のProSep Guard ColumnとProSep A High CapacityをpH7.4のリン酸緩衝生理食塩水で洗浄し、Watson Marlow社製の505Sを使用して、60rpmでポンプにかけた。内径1mmのシリコンチューブを使用し、流量は、20ml/秒とした。
Millipore社(U.K)製の.ProSep G High Capacityを、pH7.4のリン酸緩衝生理食塩水内で洗浄し、上記実施例1に記載したものと本質的に同じプロセスで、下記に示す他の結合剤を精製するために用いた。
金(BioGold )表面をコーティングしたErie Scientific社製のスライドを基板として使用した。スポットする結合剤抗体プローブのサンプルを、リン酸緩衝生理食塩水内で準備した。SpotBot(Telechem/Arrayit)またはBioRobotic MicroGrid II Arrayerを用い、200μm〜700μmの硬質ピンで、スライドをプリントした。各サンプルの複製を、各スライド上にプリントし、スライドを少なくとも1時間、空気乾燥させてからバック内に密閉し、4℃の温度で、必要となるまで保った。スライドを、リン酸緩衝生理食塩水内で軽くすすいでから、PBS−BSAブロッキング剤(リン酸緩衝生理食塩水−ウシ血清アルブミン)の容器内で、絶えず混合しながら1時間、室温で処理した。取り出す際、スライドをリン酸緩衝生理食塩水で軽くすすぎ、遠心分離器内で1分間、1000rpmで遠心分離して乾燥させた。
実施例3に従って準備した各マイクロアレイを、チャンバで覆った。被験者の血液サンプルを、リン酸緩衝生理食塩水内で、少なくとも4回洗浄した。PBS−BSA(リン酸緩衝生理食塩水−ウシ血清アルブミン)内に血液サンプルを1%のヘマトクリット値になるまで懸濁し、マイクロアレイに加える赤血球溶液を準備した。その後、450μlの赤血球溶液を、チャンバの小窓の1つからピペットでマイクロアレイのスライド上に点下し、付属のシールで小窓を密閉した。スライドをスライドボックスに入れ、室温で1時間、混合した。
Genepix Personal 4100A Scannerまたは同様のスキャナを用いて、スライドをスキャンした。赤血球の自己蛍光を検出する波長は、前に記述したように設定した。全てのスライドを、10ミクロンの画素サイズでスキャンし、BMPおよびTIFの両ファイルに保存した。
実施例3に従って準備した各マイクロアレイを、チャンバで覆った。被験者の血液サンプルを、リン酸緩衝生理食塩水内で、少なくとも4回洗浄した。PBS−BSA(リン酸緩衝生理食塩水−ウシ血清アルブミン)内に血液サンプルを1%のヘマトクリット値になるまで懸濁し、マイクロアレイに加える赤血球溶液を準備した。その後、450μlの赤血球溶液を、チャンバの小窓の1つからピペットでマイクロアレイのスライド上に点下し、付属のシールで小窓を密閉した。スライドをスライドボックスに入れ、室温で1時間、混合した。
すべての手順を、前述したものと同様に行った。本実施例において、赤血球サンプルは、抗D‘H’(LHM77/64)で感作したO型のR1r細胞を含んだ。
Claims (20)
- 被験者の赤血球が、1つ以上の特徴的な抗体/補体因子と結合していることを特徴とする疾病の検出に用いるのに適した血液検査方法であって、
−異なる特徴的な抗体/補体因子と特異的に結合する多数の結合剤を、基板上のあらかじめ定めた位置に個別に固定したマイクロアレイを提供し、
−前記マイクロアレイに、被験者から採取した血液サンプルを接触させ、
−前記結合剤を固定した1つ以上の領域から、非結合の赤血球を実質的に全て除去し、
−前記マイクロアレイと結合した赤血球の存在を検出し、
これにより、特徴的な抗体/補体因子が被験者の赤血球と結合したかどうかを判断する、
というステップからなる、血液検査方法。 - 前記結合剤が、モノクローナル抗体である、請求項1に記載の方法。
- 前記結合剤が、ポリクローナル抗体である、請求項1に記載の方法。
- 前記結合剤が、キメラ抗体である、請求項1に記載の方法。
- 前記結合剤が、単鎖抗体である、請求項1に記載の方法。
- 前記結合剤が、モノクローナル抗IgG1、モノクローナル抗IgG3 、モノクローナル抗C3から選択される、請求項1に記載の方法。
- ポリクローナル抗IgGが含まれる、請求項6に記載の方法。
- 基板上の個別の領域に、2つ以上の異なる結合剤が固定される、請求項1〜7のいずれかに記載の方法。
- 各結合剤が、多数の異なる希釈で提供される、請求項1〜8のいずれかに記載の方法。
- 各結合剤が、所与の希釈につき多数回繰り返される、請求項9に記載の方法。
- 前記基板が、ガラス、ケイ素、酸化ケイ素、金属および金属酸化物を、そのままの状態で用いて、あるいは機能性ポリマーで機能化したもので作られている、請求項1〜10のいずれかに記載の方法。
- 前記基板が、金でコーティングした基板である、請求項11に記載の方法。
- 前記金が、その表面上に結合剤の固定化が可能なように機能化されている、請求項12に記載の方法。
- 前記機能化により、金表面と結合赤血球との距離が制御可能な、請求項13に記載の方法。
- 前記マイクロアレイが、平面状または球状の表面上に形成される、請求項1〜14のいずれかに記載の方法。
- 前記基板が、膜、フィルター、チップ、スライド、ウェーハ、ファイバー、磁性または非磁性ビーズ、ゲル、チューブ、プレート、ポリマー、微粒子および毛管などの、硬質または半硬質支持体である、請求項1〜15のいずれかに記載の方法。
- 前記結合剤が、1mm未満のスポット内に固定化される、請求項1〜16のいずれかに記載の方法。
- 前記基板が、その表面上に個別のアレイを複数有し、別々のサンプルと各アレイとが、各サンプルが混合しないようなやり方で接触するよう配列される、請求項1〜17のいずれかに記載の方法。
- 前記基板表面の結合剤を付与されていない領域は、非特異的結合を最低限に抑えるため、ブロッキング剤で処理されている、請求項1〜18のいずれかに記載の方法。
- 結合赤血球細胞が、二次標識検出により検出される、請求項1〜19のいずれかに記載の方法。
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GBGB0618496.4A GB0618496D0 (en) | 2006-09-20 | 2006-09-20 | Blood typing |
PCT/GB2007/003514 WO2008035047A1 (en) | 2006-09-20 | 2007-09-16 | Blood typing |
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CN105866426B (zh) * | 2008-12-01 | 2018-11-23 | 小利兰·斯坦福大学托管委员会 | 用于检测补体结合性抗体的方法和组合物 |
WO2014151763A1 (en) | 2013-03-14 | 2014-09-25 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of detecting donor-specific antibodies and systems for practicing the same |
GB201402174D0 (en) * | 2014-02-07 | 2014-03-26 | Qbd Qs Ip Ltd | Detection method |
GB201403115D0 (en) | 2014-02-21 | 2014-04-09 | Qbd Qs Ip Ltd | Red blood cell detection |
WO2016113691A1 (en) | 2015-01-14 | 2016-07-21 | Bio-Rad Laboratories, Inc. | Blood analysis systems and methods |
US10527613B2 (en) | 2015-11-10 | 2020-01-07 | The Board Of Trustees Of The Leland Stanford Junior University | Biomarker detection methods and systems and kits for practicing same |
WO2018223014A1 (en) | 2017-06-02 | 2018-12-06 | Georgia State University Research Foundaton, Inc. | Dna-glycan conjugates and methods of use |
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NL1008738C2 (nl) * | 1998-03-27 | 1999-09-28 | Stichting Bloedvoorziening | Vaste-fase methode voor antigeen- en antistof bepalingen in de bloedgroepserologie, en testkit. |
US20070003979A1 (en) * | 1998-10-30 | 2007-01-04 | Worthington Mark O | Trackable optical discs with concurrently readable analyte material |
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EP2062055A1 (en) | 2009-05-27 |
ES2388147T3 (es) | 2012-10-09 |
JP2010504513A (ja) | 2010-02-12 |
CA2664055C (en) | 2015-06-30 |
CA2664055A1 (en) | 2008-03-27 |
US20100041565A1 (en) | 2010-02-18 |
ATE553386T1 (de) | 2012-04-15 |
GB0618496D0 (en) | 2006-11-01 |
AU2007298839A1 (en) | 2008-03-27 |
EP2062055B1 (en) | 2012-04-11 |
AU2007298839B2 (en) | 2013-01-17 |
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