JP2009506345A - 分析物を検出するためのnmr装置 - Google Patents
分析物を検出するためのnmr装置 Download PDFInfo
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- JP2009506345A JP2009506345A JP2008529259A JP2008529259A JP2009506345A JP 2009506345 A JP2009506345 A JP 2009506345A JP 2008529259 A JP2008529259 A JP 2008529259A JP 2008529259 A JP2008529259 A JP 2008529259A JP 2009506345 A JP2009506345 A JP 2009506345A
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Abstract
【解決手段】本発明の分析物検出装置は、一般的には、それぞれがNMR用微小コイルに囲まれるか、そのすぐ周囲にあり、各ウェルが、液体試料を、標的分析物が存在すると自己集合または離散する磁性ナノ粒子とともに含んでいるために、測定された液体試料のNMR特性が変化する1つ以上のウェルをもつ。本装置は、例えば、ポイント・オブ・ケア診断および/または現場使用のための携帯用装置として使用することが可能であり、または、本装置を、患者の体内において、対象とする1つ以上の生物種を継続的または間欠的に観察するために埋め込むことも可能である。
【選択図】図1
Description
(i)磁性粒子および分析物を含む液体試料を保持するためのウェルを形成する支持体であって、磁性粒子が、それに結合している結合成分を有する支持体、および、液体試料の周囲に配置されたRFコイルであって、1個以上の磁石およびRF励起を用いて形成したバイアス磁界に液体試料を曝露することによって生じるエコー応答を検出するよう構成されていて、約10μmから約1000μmの特有の寸法をもつRFコイルを有する装置;
(ii)磁性粒子および分析物を含む液体試料を保持するための複数のウェルであって、この磁性粒子が、それに結合している結合成分を有するウェル、および、各ウェルについて、ウェルの周囲に配置されたRFコイルであって、1個以上の磁石およびRF励起を用いて形成したバイアス磁界に液体試料を曝露することによって生じるエコー応答を検出するよう構成されているRFコイルを有する装置;(iii)液体試料を保持するために1つ以上のウェルを形成している支持体、および、その支持体上に配置された、上記1つ以上のウェルの内部で再構成させるための、結合成分を結合している乾燥超常磁性粒子を含む装置であって、結合成分が、液体試料中の分析物の有無または濃度に応じて、液体試料中の磁性粒子の凝集を変える働きをしている装置;(iv)液体試料を保持するための1つ以上のウェルを形成している支持体を有する装置であって、試料が磁性粒子と分析物を含み、磁性粒子が、それに結合した結合成分をもち、この結合成分が、液体試料中の上記磁性粒子の有無または濃度に応じて、液体試料中の上記磁性粒子の凝集を変える働きをし、また、ウェルの少なくとも1つが、磁界の存在下で、粒子の凝集体が、大きい方の断面の領域から小さい方の断面の領域へ移動して、凝集体とともに運ばれた分析物を濃縮するような変化する断面を有する装置;(v)磁性粒子および分析物を含む液体試料を保持するためのウェルを形成する支持体であって、磁性粒子が、それに結合している結合成分を有する支持体、および、液体試料の周囲に配置されたRFコイルであって、1個以上の磁石およびRF励起を用いて形成したバイアス磁界に液体試料を曝露することによって生じるエコー応答を検出するよう構成されているRFコイルを有し、このウェルおよびRFコイルが、少なくとも約0.1の充填率を備えるよう構成されている装置;(vi)磁性粒子および分析物を含む液体試料を保持するためのウェルを形成する支持体であって、磁性粒子が、それに結合している結合成分を有する支持体、および、液体試料の回りに配置されたRFコイルであって、1個以上の磁石およびRF励起を用いて形成したバイアス磁界に液体試料を曝露することによって生じるエコー応答を検出するよう構成されているRFコイルを有し、(A)RFコイルに囲まれている容量、(B)液体試料量の少なくとも1つが約1mLよりも少ない装置;および/または(vii)磁性粒子および分析物を含む液体試料を保持するためのウェルを形成する支持体であって、磁性粒子が、それに結合している結合成分を有する支持体、液体試料の回りに配置されたRFコイルであって、1個以上の磁石およびRF励起を用いて形成したバイアス磁界に液体試料を曝露することによって生じるエコー応答を検出するよう構成されているRFコイル、およびRFコイルと連結した電気素子であって、少なくとも部分的に、エコー応答に対応したシグナルを調整するよう構成された電気素子を有し、このRFコイルが、電気素子に対して十分な近さに配置されて、少なくとも1のQ係数を備えるが、このQ係数(線質係数)は、所定の周波数、例えば、ラーモア周波数におけるRFコイルの抵抗に対するその誘導リアクタンスの割合である装置。上記実施形態の構成装置についての説明は、本発明の本実施形態にも適用することができる。
オランザピン;組み換え甲状腺刺激ホルモン(r−TSH);トポテカン;アシクロビルナトリウム;アルデスロイキン;アテノロール;硫酸ブレオマイシン、ヒトカルシトニン;サケカルシトニン;カルボプラチン;カルムスチン;ダクチノマイシン、ダウノルビシンHCl;ドセタキセル;ドキソルビシンHCl;エポエチンアルファ;エトポシド(VP−16);フルオロウラシル(5−FU);ガンシクロビルナトリウム;硫酸ゲンタマイシン;インターフェロンα;酢酸ロイプロリド;メペリジンHCl;メタドンHCl;メトトレキセートナトリウム;パクリタキセル;ラニチジンHCl;硫酸ビンブラスチン;ならびにジドブジン(AZT)。
102 バイアス磁石
104 バイアス磁界
106 液体試料
108 ウェル
110 RFコイル
112 RFオシレータ
114 増幅装置
Claims (106)
- 磁性粒子および分析物を含む液体試料を入れるためのウェルを形成する支持体であって、前記磁性粒子が、それに結合した結合成分を有する支持体、および
1個以上の磁石とRF励起を用いて発生させたバイアス磁界に前記液体試料を曝露することによって生じるエコー応答を検出するように構成され、前記液体試料の周囲に配置されたRFコイルであって、約10μmから約1000μmという特有の寸法をもつRFコイル
を有する分析物検出用装置。 - 請求項1において、前記特有の寸法が直径である分析物検出用装置。
- 請求項1において、前記特徴的な寸法が長さまたは深さである分析物検出用装置。
- 請求項1において、前記ウェルおよび前記RFコイルは、充填率が少なくとも0.1を備えるように構成されている分析物検出用装置。
- 請求項1において、前記ウェルおよび前記RFコイルは、充填率が少なくとも0.7を備えるように構成されている分析物検出用装置。
- 請求項1において、前記ウェルおよび前記RFコイルは、充填率が少なくとも1を備えるように構成されている分析物検出用装置。
- 請求項1において、
(i)前記RFコイルに囲まれた体積、および
(ii)前記液体試料量
のうち少なくとも1つが1mLよりも少ない分析物検出用装置。 - 請求項1において、
(i)前記RFコイルに囲まれた体積、および
(ii)前記液体試料量
のうち少なくとも1つが100μLよりも少ない分析物検出用装置。 - 請求項1において、前記RFコイルと連係する電気素子であって、前記エコー応答に対応したシグナルを少なくとも部分的に調整するために構成された電気素子をさらに有する分析物検出用装置。
- 請求項9において、前記RFコイルが、少なくとも1というQ係数を備えるように前記電気素子に十分に近接して配置されている分析物検出用装置。
- 請求項9において、前記RFコイルが、少なくとも10というQ係数を備えるように前記電気素子に十分に近接して配置されている分析物検出用装置。
- 請求項9において、前記RFコイルが、前記支持体と一体化して前記ウェルの周囲に配置されている分析物検出用装置。
- 請求項9において、前記RFコイルが、前記電気素子の1センチメートル以内に配置されている分析物検出用装置。
- 請求項9において、前記RFコイルが、前記電気素子の1ミリメートル以内に配置されている分析物検出用装置。
- 請求項9において、前記電気素子が、
(i)前記シグナルの増幅、
(ii)前記シグナルの整流、および
(iii)前記シグナルのデジタル化
のうち少なくとも1つを行うよう構成されている分析物検出用装置。 - 請求項1において、前記結合成分が、前記分析物の有無または濃度に応じて前記磁性粒子の凝集状態を変える働きをする分析物検出用装置。
- 請求項1において、前記磁性粒子が、その表面上に前記結合成分をもつ超常磁性ナノ粒子である分析物検出用装置。
- 請求項1において、前記バイアス磁界が実質的に一様である分析物検出用装置。
- 請求項1において、前記バイアス磁界が空間勾配をもつ分析物検出用装置。
- 請求項1において、前記1個以上の磁石の少なくとも1個を有する分析物検出用装置。
- 請求項1において、前記RF励起が、前記ウェルの周囲に配置された前記RFコイルとは別のRF励起コイルを介して伝達される分析物検出用装置。
- 請求項1において、前記RF励起が、前記ウェルの周囲に配置された前記RFコイルを介して伝達される分析物検出用装置。
- 請求項1において、チップ上に作製されている分析物検出用装置。
- 請求項23において、MEMSプロセスで作製されている分析物検出用装置。
- 請求項23において、前記RFコイルが、前記チップの表面上に置かれている分析物検出用装置。
- 請求項1において、前記RFコイルが巻きソレノイドコイルである分析物検出用装置。
- 請求項1において、前記RFコイルが平面コイルである分析物検出用装置。
- 請求項1において、前記RFコイルがMEMSソレノイドコイルである分析物検出用装置。
- 請求項1において、前記磁性粒子が前記ウェルの表面上に置かれている分析物検出用装置。
- 請求項29において、前記磁性粒子が、プリンタとともに前記ウェルの表面上に置かれている分析物検出用装置。
- 請求項29において、液体を導入すると前記磁性粒子を再構成することができる分析物検出用装置。
- 請求項29において、前記磁性粒子が凍結乾燥されている分析物検出用装置。
- 請求項1において、少なくとも1つの前記結合成分が、
(i)前記分析物、
(ii)前記結合成分の別のもの、および
(iii)前記液体試料中の凝集誘導分子
のうち少なくとも1つに結合する働きをし、それによって、多重結合した磁性粒子の凝集体を、前記液体試料中における前記分析物の有無または濃度に応じて生じさせる分析物検出用装置。 - 請求項33において、前記凝集体が、その最も大きな寸法で100nmから500nmというおおよそのサイズをもつ分析物検出用装置。
- 請求項33において、前記凝集体が、前記結合成分を介して結合した2個から20個の磁性粒子を有する分析物検出用装置。
- 請求項1において、前記磁性粒子が、それらの最も大きな寸法で5nmから500nmの平均サイズをもつ分析物検出用装置。
- 請求項1において、多重結合した磁性粒子の凝集体が、前記液体試料中における前記分析物の有無または濃度に応じて離散する分析物検出用装置。
- 請求項1において、前記結合成分が、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、ペプチド、ポリペプチド、タンパク質、炭水化物、多糖体、ウイルス、および細菌のうち少なくとも1つを含んでいる分析物検出用装置。
- 請求項1において、前記分析物が、タンパク質、ペプチド、ポリペプチド、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、RNA、DNA、抗体、生物、ウイルス、細菌、炭水化物、多糖体、およびグルコースのうち少なくとも1つを含んでいる分析物検出用装置。
- 請求項1において、前記エコー応答に対応する前記シグナルを受信するよう構成された読取装置をさらに有する分析物検出用装置。
- 請求項40において、前記読取装置が、前記シグナルを処理するための電気素子、および分析物の有無または濃度を表示するためのディスプレイを有する分析物検出用装置。
- 請求項40において、前記読取装置が、
(i)前記バイアス磁界を発生させるための磁石、および
(ii)前記RF励起を提供するためのRF励起コイル
のうち少なくとも1つを有する分析物検出用装置。 - 請求項40において、前記読取装置が、前記エコー応答に対応する前記シグナルによるT2緩和時間の変化を測定する分析物検出用装置。
- 請求項1において、携帯可能な分析物検出用装置。
- 請求項1において、埋め込み可能であり、皮膚貫通ワイヤなしで操作可能な分析物検出用装置。
- 請求項1において、重さが1キログラムよりも少ない分析物検出用装置。
- 磁性粒子および分析物を含む液体試料を入れるための複数のウェルを有し、前記磁性粒子が、それに結合した結合成分をもち、また、前記ウェルの各々について、
1個以上の磁石とRF励起を用いて発生させたバイアス磁界に前記ウェル中の液体試料を曝露することによって生じるエコー応答を検出するよう構成された、前記ウェルの周囲に配置されたRFコイルを有する分析物検出用装置。 - 請求項47において、前記ウェルの各々について、前記RFコイルと連係する電気素子であって、前記エコー応答に対応したシグナルを少なくとも部分的に調整するために構成された電気素子をさらに有する分析物検出用装置。
- 請求項47において、前記ウェルが配列に配置されている分析物検出用装置。
- 請求項49において、前記配列が実質的に2次元である分析物検出用装置。
- 請求項49において、前記配列が3次元である分析物検出用装置。
- 請求項47において、前記複数のウェルの中に液体の分配が行われるように構成されている分析物検出用装置。
- 請求項47において、少なくとも1個のウェルが、前記分析物によって実質的に影響を受けない既知の特性をもち、較正に使用されている分析物検出用装置。
- 請求項47において、複数の分析物を検出するために、異なった結合成分をもつ磁性粒子が、異なったウェルの中に入れられている分析物検出用装置。
- 請求項47において、重複測定のために、同じ結合成分をもつ磁性粒子が、異なったウェルの中に入れられ、それによって正確さを向上させる分析物検出用装置。
- 請求項47において、前記液体試料中の異なった分析物濃度を検出するために、同じ結合成分をもつ磁性粒子が、異なったウェルの中に入れられている分析物検出用装置。
- 請求項47において、異なったウェルでは、その中に入れられた結合成分の濃度が異なっている分析物検出用装置。
- 請求項47において、異なった結合成分をもつ磁性粒子が、前記分析物を検出するために異なったウェルの中に入れられ、前記異なった結合成分が、前記分析物の濃度に比例して前記磁性粒子の凝集または離散を促進する分析物検出用装置。
- 請求項48において、前記ウェルの各々について、前記各RFコイルが、前記RFコイルと連係している前記電気素子の1センチメートル以内に配置されている分析物検出用装置。
- 請求項48において、前記電気素子が、
(i)前記シグナルの増幅、
(ii)前記シグナルの整流、および
(iii)前記シグナルのデジタル化
のうち少なくとも1つを行うよう構成されている分析物検出用装置。 - 請求項48において、前記RFコイルが、少なくとも1というQ係数を備えるよう前記電気素子に十分に近接して配置されている分析物検出用装置。
- 請求項47において、基質が、前記複数のウェルを形成し、前記RFコイルの各々が、前記基質と一体化して、その各ウェルの周囲に配置されている分析物検出用装置。
- 請求項47において、前記RF励起が、前記各ウェルの周囲に配置された前記各RFコイルとは別のRF励起コイルを介して伝達される分析物検出用装置。
- 請求項63において、前記RF励起コイルが、前記複数のウェルの周囲に配置されている分析物検出用装置。
- 請求項47において、MEMSプロセスで作製されている装置。
- 請求項47において、前記磁性粒子が、前記複数のウェルの1つ以上の表面上に置かれている分析物検出用装置。
- 請求項66において、液体を導入すると前記磁性粒子を再構成することができる分析物検出用装置。
- 請求項47において、前記分析物が、タンパク質、ペプチド、ポリペプチド、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、RNA、DNA、抗体、生物、ウイルス、細菌、炭水化物、多糖体、およびグルコースのうち少なくとも1つを含んでいる分析物検出用装置。
- 請求項47において、前記結合成分が、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、ペプチド、ポリペプチド、タンパク質、炭水化物、多糖体、ウイルス、および細菌のうち少なくとも1つを含んでいる分析物検出用装置。
- 請求項47において、前記ウェルの各々について、前記各ウェルからの前記エコー応答に対応するシグナルを受信するよう構成された読取装置をさらに有する分析物検出用装置。
- 請求項70において、前記受信装置が、前記シグナルを処理するための電気素子、および分析物の有無または濃度を表示するためのディスプレイを有する分析物検出用装置。
- 液体試料を入れるために1つ以上のウェルを形成する支持体、および
前記支持体の上に配置され、前記1つ以上のウェルの中で再構成を行わせるために、結合成分をそれに結合させている乾燥超常磁性ナノ粒子を有する装置であって、
前記結合成分が、前記液体試料中における前記分析物の有無または濃度に応じて、前記液体試料中の前記磁性粒子の凝集状態を変える働きをする装置。 - 請求項72において、前記1つ以上のウェルの各々について、前記ウェルの周囲に配置されたRFコイル、および前記RFコイルと連係している電気素子をさらに有し、
前記RFコイルが、1個以上の磁石とRF励起を用いて発生させたバイアス磁界に前記ウェル中の液体試料を曝露することによって生じるエコー応答を検出するよう構成されていて、
前記電気素子が、前記エコー応答に対応したシグナルを少なくとも部分的に調整するよう構成されている装置。 - 請求項72において、前記支持体が、前記ウェルの配列を形成している装置。
- 請求項72において、分析物検出システムの構成要素である装置。
- 請求項73において、前記RF励起を伝達するためのRF励起コイルをさらに有し、前記RF励起コイルが、前記1つ以上のウェルの周囲に配置された前記1つ以上のRFコイルとは別のものである装置。
- 請求項73において、前記1つ以上のウェルの各々について、前記ウェル、および前記ウェルの周囲に配置された前記RFコイルは、充填率が少なくとも0.7を備えるよう構成されている装置。
- 請求項73において、前記1つ以上のウェルの各々について、前記各RFコイルが、前記RFコイルと連係している前記電気素子の1センチメートル以内に配置されている装置。
- 請求項73において、前記電気素子が、
(i)前記シグナルの増幅、
(ii)前記シグナルの整流、および
(iii)前記シグナルのデジタル化
のうち少なくとも1つを行うよう構成されている装置。 - 請求項72において、前記分析物が、タンパク質、ペプチド、ポリペプチド、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、RNA、DNA、抗体、生物、細菌、炭水化物、多糖体、ウイルス、およびグルコースのうち少なくとも1つを含んでいる装置。
- 請求項72において、前記結合成分が、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、ペプチド、ポリペプチド、タンパク質、炭水化物、細菌、ウイルス、および多糖体のうち少なくとも1つを含んでいる装置。
- 請求項73において、前記ウェルの各々について、前記各ウェルからの前記エコー応答に対応するシグナルを受信するよう構成された読取装置をさらに有する装置。
- 液体試料を入れるための1つ以上のウェルを形成する支持体であって、前記試料が、磁性粒子および分析物を含み、前記磁性粒子が、それに結合した結合成分を有する支持体を有する装置であって、
前記液体試料中における前記分析物の有無または濃度に応じて、前記結合成分が前記磁性粒子の凝集状態を変える働きをし、かつ、少なくとも1つの前記ウェルが、磁界存在下で、前記粒子の凝集体が、大きい方の断面の領域から小さい方の断面の領域へ移動して、前記凝集体とともに運ばれた前記分析物を濃縮するような変化する断面を有している装置。 - 請求項83において、前記1つ以上のウェルの各々について、前記ウェルの周囲に配置されたRFコイル、および前記RFコイルと連係している電気素子を有し、前記RFコイルが、1個以上の磁石とRF励起を用いて発生させたバイアス磁界に前記ウェル中の液体試料を曝露することによって生じるエコー応答を検出するよう構成されていて、前記電気素子が、前記エコー応答に対応したシグナルを少なくとも部分的に調整するよう構成されている装置。
- 請求項83において、少なくとも1つの前記結合成分が、
(i)前記分析物、
(ii)前記結合成分の別のもの、および
(iii)前記液体試料中の凝集誘導分子
のうち少なくとも1つに結合する働きをし、それによって、前記凝集を生じさせる装置。 - 請求項83において、前記結合成分が、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、ペプチド、ポリペプチド、タンパク質、炭水化物、多糖体、ウイルス、および細菌のうち少なくとも1つを含んでいる装置。
- 請求項83において、前記分析物が、タンパク質、ペプチド、ポリペプチド、アミノ酸、核酸、オリゴヌクレオチド、治療剤、治療剤の代謝産物、RNA、DNA、抗体、生物、ウイルス、細菌、炭水化物、多糖体、およびグルコースのうち少なくとも1つを含んでいる装置。
- 磁性粒子および分析物を含む液体試料を入れるためのウェルを形成する支持体であって、前記磁性粒子が、それに結合した結合成分を有する支持体、および
1個以上の磁石とRF励起を用いて発生させたバイアス磁界に前記液体試料を曝露することによって生じるエコー応答を検出するよう構成され、前記ウェルおよび前記RFコイルが、充填率少なくとも0.1を備えるよう構成されている、前記液体試料の周囲に配置されたRFコイル
を有する分析物検出用装置。 - 請求項88において、前記ウェルおよび前記RFコイルが、充填率少なくとも0.7を備えるように構成されている分析物検出用装置。
- 請求項88において、前記ウェルおよび前記RFコイルは、充填率が1を備えるように構成されている分析物検出用装置。
- 磁性粒子および分析物を含む液体試料を入れるためのウェルを形成する支持体であって、前記磁性粒子が、それに結合した結合成分を有する支持体、および
1個以上の磁石とRF励起を用いて発生させたバイアス磁界に前記液体試料を曝露することによって生じるエコー応答を検出するよう構成されている、前記液体試料の周囲に配置されたRFコイル
を有する分析物検出用装置であって、
(i)前記RFコイルに囲まれた体積、および
(ii)前記液体試料量
のうち少なくとも1つが1mLよりも少ない分析物検出用装置。 - 請求項91において、
(i)前記RFコイルに囲まれた体積、および
(ii)前記液体試料量
のうち少なくとも1つが100μLよりも少ない分析物検出用装置。 - 磁性粒子および分析物を含む液体試料を入れるためのウェルを形成する支持体であって、前記磁性粒子が、それに結合した結合成分を有する支持体、
1個以上の磁石とRF励起を用いて発生させたバイアス磁界に前記液体試料を曝露することによって生じるエコー応答を検出するよう構成されている、前記液体試料の周囲に配置されたRFコイル、および
前記RFコイルと連係する電気素子であって、前記エコー応答に対応したシグナルを少なくとも部分的に調整するために構成された電気素子
を有する分析物検出用装置であって、
前記RFコイルが、少なくとも1というQ係数を備えるように前記電気素子に十分に近接して配置されている分析物検出用装置。 - 請求項93において、前記RFコイルが、少なくとも10というQ係数を備えるように前記電気素子に十分に近接して配置されている分析物検出用装置。
- 請求項93において、前記RFコイルが基質と一体化して、前記ウェルの周囲に配置されている分析物検出用装置。
- 請求項93において、前記RFコイルが、前記電気素子の1センチメートル以内に配置されている分析物検出用装置。
- 請求項93において、前記RFコイルが、前記電気素子の1ミリメートル以内に配置されている分析物検出用装置。
- 請求項1〜97のいずれか一項記載の装置を用いて、試料中の1つ以上の分析物を測定する方法。
- 請求項98において、前記1つ以上の分析物が、複数の生物活性物質を含んでいる方法。
- 請求項98において、前記試料が、研究用試料、細胞試料、および生物由来試料のうち少なくとも1つを含んでいる方法。
- 請求項98において、生体内で行われる方法。
- 請求項98において、前記測定工程が、前記1つ以上の分析物の濃度を測定することを含む方法。
- 請求項98において、前記測定工程が、前記1つ以上の分析物の有無を検出することを含む方法。
- 請求項98において、前記測定工程が、前記1つ以上の分析物を継続的に観察することを含む方法。
- 請求項98において、前記測定工程が、前記1つ以上の分析物を半継続的に観察することを含む方法。
- 請求項98において、前記測定工程が、前記1つ以上の分析物を生体内で継続的に観察することを含む方法。
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US20120107839A1 (en) | 2012-05-03 |
US20210048491A1 (en) | 2021-02-18 |
US20110020787A1 (en) | 2011-01-27 |
US20070116602A1 (en) | 2007-05-24 |
US20170299668A1 (en) | 2017-10-19 |
WO2007027843A2 (en) | 2007-03-08 |
AU2006284832A8 (en) | 2008-05-01 |
US20090134869A1 (en) | 2009-05-28 |
EP1932009A2 (en) | 2008-06-18 |
US7564245B2 (en) | 2009-07-21 |
US8310231B2 (en) | 2012-11-13 |
US8102176B2 (en) | 2012-01-24 |
JP5295769B2 (ja) | 2013-09-18 |
WO2007027843A3 (en) | 2007-08-02 |
CA2620861A1 (en) | 2007-03-08 |
US20110021374A1 (en) | 2011-01-27 |
EP1932009B1 (en) | 2014-02-12 |
US8310232B2 (en) | 2012-11-13 |
US20110020953A1 (en) | 2011-01-27 |
US20130229179A1 (en) | 2013-09-05 |
US20110018538A1 (en) | 2011-01-27 |
US8624592B2 (en) | 2014-01-07 |
US8334693B2 (en) | 2012-12-18 |
US20120313639A1 (en) | 2012-12-13 |
US20110020788A1 (en) | 2011-01-27 |
US8344731B2 (en) | 2013-01-01 |
AU2006284832A1 (en) | 2007-03-08 |
AU2006284832B2 (en) | 2011-06-02 |
CA2620861C (en) | 2016-07-05 |
US8704517B2 (en) | 2014-04-22 |
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