JP6823699B2 - 生物医学的な感知及び検出のための粒子を含む溶液中の粒子の空間的な分離 - Google Patents
生物医学的な感知及び検出のための粒子を含む溶液中の粒子の空間的な分離 Download PDFInfo
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Description
・1つの工程で、単一の一体化されたデバイスにより、流体が止められている間あるいは流体が流れている間に流体の局所的な領域内に連続的に音響力を加え、止められている又は流れている流体から粒子が分離されている流体中の分析物を検出器によって測定することで、微粒子担持流体における粒子分離効率が向上すること、
・流れている又は止められているサンプル中の微粒子及び流体を1つの工程で分離する、すなわち、例えば細胞である粒子を単一段階で分離し、「流れている間の分離」に使用されている多段階分離の必要がないこと、
・分析測定のために血漿を収集するための別個のデバイス、例えば遠心分離機又はフィルタ、又は収集された血漿を分析する別個の分析物検出デバイスを省略することができること、
・音響力を加えてから分析物を分析した後に、分離されている例えば赤血球(RBC)を
元に戻して全血を再構成し、血液の完全性、例えば、ヘマトクリット値、血液成分、RBCの完全性を維持することができること、
・全血の他の測定値、例えば全血の粘性について、血漿及びRBCを追加的に再混合する必要なしに、(粒子が可逆的に分離されるので)全血サンプルを再利用することができること、
・分析に必要なサンプル量が、1マイクロリットル〜10ミリリットルと、少量ですむこと、
・本発明に係るマイクロ流体デバイスにおける、音響手段(acoustics)、流体手段(fluidics)、及び例えば光学検出器である検出器の製造及び動作が単純であること。
・例えばビーズベース(bead-based)のウイルス検出、又はバクテリア検出など、リポータビーズ(reporter bead)を用いた、粒子ベースの化学アッセイの分野、
・血液サンプル中、他の体液サンプル中、又はこれに限定されないが腫瘍などの組織から得られる細胞分画中の循環腫瘍細胞(CTC)など、細胞懸濁液を用いた他の細胞ベースア
ッセイの分野、
でも使用可能である。
図3A及び図3Bは、対象の標的分析物についての、全血などの複合粒子担持流体(複合流体)16の分析のための本発明に係るシステム10の全体的な原理及び一実施形態を示している。システム10は、マイクロ流体デバイス構造22を含む。マイクロ流体デバイス構造22は、1つ又は複数のマイクロチャネル12と、複合粒子担持流体16の導入のための少なくとも1つのマイクロチャネル12と流体連通する少なくとも1つのサンプルポート14とを含む。マイクロチャネル12は、複合粒子担持流体16中の分析物を検出する少なくとも1つの検出器19、及び少なくとも1つの検出場所18又は領域を含む。少なくとも1つの音響トランスデューサ20は、マイクロ流体デバイス22に組み込まれ、音響波24を、マイクロチャネル12の検出器領域18内の、例えば全血である複合流体16のカラム26内へと送る。検出器19による標的分析物の分析のために、流体カラム16の検出器領域18に加えられる音響力24によって、複合流体16中の粒子27、例えばRBC27が分離され、検出器領域18内に、例えば血漿である、実質的に粒子を含まない流体28が生成される。
Claims (11)
- 全血中の分析物を分析する方法であって、
全血を分析デバイスのマイクロチャネルに導入することと、
音響力が前記全血中の血漿から血液細胞を可逆的に分離するよう、前記マイクロチャネルの検出領域の前記全血に前記音響力を加え、前記マイクロチャネル中に実質的に粒子を含まない血漿の領域を生成し、前記実質的に粒子を含まない血漿の領域が、前記検出領域を含むことと、
前記マイクロチャネルの前記検出領域における血漿分析物を検出するよう構成された検出器を適用することと、
前記音響力を加えながら、前記検出器で、前記検出領域の前記血漿分析物を光学的に検出することと、
を含む方法。 - 前記血漿分析物の光学的検出の間、前記マイクロチャネル中の前記血漿の流れを、前記マイクロチャネルの前記検出領域に抑制することをさらに含む、請求項1に記載の方法。
- 前記音響力を解放し、前記マイクロチャネル中に再構成された全血を形成することと、
前記検出領域の下流で前記再構成された全血を収集することと、
をさらに含む、請求項1に記載の方法。 - 前記流れが、ポンプ、バルブ、及び流れレギュレータからなる群から選択される流れ抑制部で抑制される、請求項2に記載の方法。
- 前記検出器が、前記実質的に粒子を含まない血漿中の遊離ヘモグロビンを検出する、請求項1に記載の方法。
- 前記音響力が超音波定在波を含む、請求項1に記載の方法。
- 前記音響力が、前記検出器に組み込まれた音響トランスデューサによって生成され、前記検出器が測光検出装置を備える、請求項1に記載の方法。
- 前記音響力が表面音響波を含む、請求項1に記載の方法。
- 前記音響力がバルク音響波を含む、請求項1に記載の方法。
- 前記音響力が、前記検出器に組み込まれた音響トランスデューサによって生成され、前記検出器が蛍光測定システムを備える、請求項1に記載の方法。
- 前記音響力が、前記検出器に組み込まれた音響トランスデューサによって生成され、前記検出器が時間分解蛍光測定システムを備える、請求項1に記載の方法。
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