JP6607945B2 - 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、実質的に無粒子の流体28が生成される。
Claims (16)
- 血漿及び血球を含む全血中の一又は複数の血漿分析物の分析のためのデバイスであって、
前記全血を収容するよう構成されたマイクロチャネルと、
前記マイクロチャネルの血漿分析物検出領域中の前記全血に対して音響力を生成するよう構成された音響トランスデューサであって、前記音響力が、前記全血を分離し、前記血漿分析物検出領域に実質的に細胞を含まない血漿を生成し、前記マイクロチャネル中における前記分離が可逆的である、音響トランスデューサと、
前記音響トランスデューサと一体化された検出器であって、前記音響力が前記全血に加えられている間、前記マイクロチャネルの前記血漿分析物検出領域の前記分離された実質的に細胞を含まない血漿における前記一又は複数の血漿分析物を検出するよう構成された検出器と
を備える、デバイス。 - 前記マイクロチャネルと連通し、前記マイクロチャネル中の前記全血の流れを抑制するよう構成された流体流れ抑制部をさらに備える、請求項1に記載のデバイス。
- 前記音響力が音響波により生成され、前記音響波が、超音波定在波、表面音響波、バルク音響波、及び音響波からなる群から選択される、請求項1に記載のデバイス。
- 複数の音響トランスデューサと、複数の血漿分析物検出領域と、複数の血漿分析物検出器と、をさらに備える、請求項1に記載のデバイス。
- 前記血漿分析物の分析後に血漿を収集するための血漿コレクタをさらに備える、請求項1に記載のデバイス。
- 前記血漿コレクタが、マイクロチャネル、ポケット、ダイラテーション、チャンバ及びキャビティからなる群から選択される、請求項5に記載のデバイス。
- 全血中の分析物の分析方法であって、
前記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、
前記マイクロチャネルの血漿分析物検出領域において前記全血に、音響トランスデューサにより生成された音響力を加えることと、
前記血漿分析物検出領域において前記全血に前記音響力を加えている間に、前記全血を可逆的に分離し、実質的に細胞を含まない血漿を生成することと、
前記マイクロチャネルの前記血漿分析物検出領域内に、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、
前記血漿分析物検出領域で血漿から可逆的に分離された血球に音響力を加えている間、前記血漿分析物検出領域で前記検出器によって前記血漿分析物を光学的に検出することと、
を含む、方法。 - 前記血漿分析物を光学的に検出する間、前記血漿分析物検出領域において、前記マイクロチャネル内の前記全血の流れを抑制することをさらに含む、請求項7に記載の方法。
- 前記血漿分析物検出領域の下流で前記全血を収集することをさらに含む、請求項7に記載の方法。
- ポンプ、バルブ、及び流量レギュレータからなる群から選択される流れ抑制部によって、前記流れが抑制される、請求項8に記載の方法。
- 前記検出器がヘモグロビンを検出する、請求項7に記載の方法。
- 前記音響力が音響波から生成され、前記音響波が、超音波定在波、表面音響波、及びバルク音響波からなる群から選択される、請求項7に記載の方法。
- 前記検出器が、測光検出装置、蛍光測定システム、及び時間分解蛍光測定システムからなる群から選択される、請求項7に記載の方法。
- 前記検出器が光学検出器を備える、請求項1に記載のデバイス。
- 前記検出器が、ヘモグロビン検出器を備える、請求項1に記載のデバイス。
- 前記流れ抑制部が、ポンプ、バルブ、及び流量レギュレータからなる群から選択される、請求項2に記載のデバイス。
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US20160202237A1 (en) | 2016-07-14 |
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