JP6581566B2 - 時間分解レーザ誘起蛍光分光システム及びその使用 - Google Patents
時間分解レーザ誘起蛍光分光システム及びその使用 Download PDFInfo
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Description
本発明は、National Institutes of Neurological Disorders and Strokeによって与えられた補助金交付番号.NS060685の下での政府支援でなされた。米国政府は、本発明に対して一定の権利を有する。
本発明は、励起シグナルに応答して生体サンプルからの発光を分析することによって生体サンプルを特徴付けるシステムを提供する。システムは、最初に生体サンプルにレーザインパルスを放射して生体サンプルに応答発光を生じさせる。システムは、次いで、波長分割装置を用いて応答発光を異なる中心波長のスペクトルバンドの組に分割する。次いで、各スペクトルバンドが光学検出器に異なる時点で届くようにスペクトルバンドの組に時間的な遅延が適用され、これにより、光学検出器が各スペクトルバンドの応答発光を別々に時間的に分解することが可能となる。次いで、遅延したスペクトルバンドが、光学検出器の単一の検出窓内でシステムによって捕捉される。その後、捕捉されたスペクトルバンドが処理される。
[本発明1001]
励起時の生体サンプルからの蛍光発光を分析することによって生体サンプルを特徴付けるためのシステムであって、
(i)励起ファイバ(ExF)を介して生体サンプルに接続されるレーザ光源であって、前記レーザが、前記生体に応答蛍光シグナルを生じさせるために前記生体サンプルに所定の波長のレーザパルスを放射するように構成される、レーザ光源と、
(ii)前記サンプルから前記蛍光シグナルを収集し、前記シグナルをデマルチプレクサにリレーする、集光ファイバ(CF)と、
(iii)スペクトルバンドを得るべく前記CFからの前記シグナルを所定の波長で分割するために波長分割フィルタを備えるデマルチプレクサと、
(iv)光遅延装置と
を備える、システム。
[本発明1002]
前記シグナルがデジタル化される前に、前記シグナルが光電子増倍管を通過した後で前記シグナルを増幅するために、前置増幅器を備える光電子増倍管をさらに備える、本発明1001のシステム。
[本発明1003]
前記光電子増倍管から受信したシグナルをデジタル化するためのデジタイザと、前記シグナルを処理及び表示するコンピュータシステムをさらに備える、本発明1002のシステム。
[本発明1004]
前記光遅延装置が、前記デマルチプレクサからの前記スペクトルバンドを前記遅延装置に連結するように適合され、単一のショットで複数の波長を捕捉するように、前記スペクトルバンドが前記遅延装置を通り、かつ、前記スペクトルバンドが遅延装置を通る際に制御された時間遅延を導入することを可能にする、本発明1001のシステム。
[本発明1005]
前記集光ファイバが単一のバンドルを形成する、本発明1001のシステム。
[本発明1006]
前記デマルチプレクサが、入射シグナルを、355nm(360未満)、365〜410nm、410〜450nm、450〜480nm、500〜560nm、560〜600nm、及び600nmを超える波長で分割する、本発明1001のシステム。
[本発明1007]
励起時の生体サンプルからの蛍光シグナルの発光を分析することによって生体サンプルを特徴付けるための方法であって、
(i)生体に応答蛍光シグナルを生じさせるために前記生体サンプルに所定の波長のレーザパルスを放射することと、
(ii)前記サンプルから前記蛍光シグナルを収集することと、
(iii)スペクトルバンドを得るべく前記シグナルを所定の波長で分割することと、
(iv)前記スペクトルバンドを時間遅延機構に通すことと、
(v)時間遅延したスペクトルバンドを得ることと、
(vi)前記時間遅延したスペクトルバンドシグナルを処理することと
を含む、方法。
[本発明1008]
前記シグナルを処理することが、光電子増倍管から受信した前記シグナルをデジタル化するために前記シグナルをデジタイザに通して、前記シグナルを処理及び表示するためにコンピュータシステムに渡すことを含む、本発明1007の方法。
[本発明1009]
前記シグナルを分割することが、入射シグナルをデマルチプレクサで355nm(365nm未満)、365〜410、410〜450nm、450〜480nm、500〜560nm、560〜600nm、及び600nmを超える波長で分割することを含む、本発明1007の方法。
[本発明1010]
前記蛍光シグナルが生体分子によって発光される、本発明1007の方法。
[本発明1011]
前記生体分子が、PLP−GAD(ピリドキサル−5'−リン酸(PLP)グルタミン酸デカルボキシラーゼ(GAD))、結合NADH、遊離NADH、フラビンモノヌクレオチド(FMN)リボフラビン、フラビンアデニンジヌクレオチド(FAD)リボフラビン、リポピグメント、内因性ポルフィリン、又はこれらの組み合わせのうちのいずれか1つ以上である、本発明1010の方法。
[本発明1012]
本発明1007の方法によって組織の生体分子からの蛍光シグナルの発光を分析することを含む組織生存性を判定するための方法であって、正常な対象と比較しての対象の生体分子の蛍光の増加が、低い組織生存性を示す、方法。
[本発明1013]
本発明1007の方法によって蛍光シグナルの発光を分析することを含む、細胞の代謝を連続的にモニタリングするための方法。
[本発明1014]
本発明1007の方法によって生体分子からの蛍光シグナルの発光を分析することを含む、血漿中の薬剤レベル又は代謝産物レベルを判定するための方法。
[本発明1015]
前記生体分子がNADHである、本発明1014の方法。
[本発明1016]
NADHが、遊離型、結合型、又はこれらの組み合わせである、本発明1015の方法。
本明細書で挙げられたすべての引用文献は、引用によりそれらの全体があたかも全て記載されているかのように組み込まれる。他に定めのない限り、本明細書で用いられる技術用語及び科学用語は、この発明が属する技術分野の当業者によって通常理解されるのと同じ意味をもつ。Allen et al., Remington: The Science and Practice of Pharmacy 22nd ed., Pharmaceutical Press (September 15, 2012)、Hornyak et al., Introduction to Nanoscience and Nanotechnology, CRC Press (2008)、Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology 3rd ed., revised ed., J.Wiley & Sons (New York, NY 2006)、Smith, March's Advanced Organic Chemistry Reactions, Mechanisms and Structure 7th ed., J.Wiley & Sons (New York, NY 2013)、Singleton, Dictionary of DNA and Genome Technology 3rd ed., Wiley−Blackwell (November 28, 2012)、及びGreen and Sambrook, Molecular Cloning: A Laboratory Manual 4th ed., Cold Spring Harbor Laboratory Press (Cold Spring Harbor, NY 2012)は、本願で用いられる用語の多くへの一般的な指針を当業者に提供する。抗体をどのようにして調製するかについての参考文献に関しては、Greenfield, Antibodies A Laboratory Manual 2nd ed., Cold Spring Harbor Press (Cold Spring Harbor NY, 2013)、Kohler and Milstein, Derivation of specific antibody−producing tissue culture and tumor lines by cell fusion, Eur.J.Immunol.1976 Jul, 6(7):511−9、Queen and Selick, Humanized immunoglobulins, U.S.Patent No.5,585,089 (1996 Dec)、及びRiechmann et al., Reshaping human antibodies for therapy, Nature 1988 Mar 24, 332(6162):323−7を参照されたい。
励起光源はパルスレーザ100である。パルスレーザからの出力パルスは、サンプルを損傷させずに生体サンプル101を励起するのに適する所定の波長及び出力レベルで生体サンプル上に放射される。パルスレーザは、各レーザインパルス出力への正確なタイミングを提供する内部又は外部パルスコントローラ装置又はデジタル遅延装置又はトリガ装置102によって制御される。この正確なタイミングは、フォトダイオードを用いてパルス毎にチェックされ、アナログ−デジタル変換器装置、例えばNI PCIe−6320を用いて更新される。一実施形態では、パルスレーザは、生体サンプルを励起するために紫外(UV)光パルスを放出する。別の実施形態では、パルスレーザは、生体サンプルを励起するために可視又は近赤外光パルスを放出する。
図2は、波長分割装置(デマルチプレクサ、デマクサ)の概略を示す。生体サンプルからのレーザ誘起発光シグナル(広範囲の波長を含む)が集光ファイバによって収集され、集光ファイバは、放出されたシグナルを波長分割装置の方に運ぶ。
図1に示されるように、波長分割装置からの各分解された波長成分は、対応する遅延装置に連結され、その後、対応する遅延装置において所定の量の遅延を経験する。種々の実施形態において、遅延装置は、異なる長さL1、L2、L3、L4などを有する光ファイバである。特定の実施形態では、光ファイバの長さは、約5フィート、55フィート、115フィート、165フィート、215フィート、265フィート、及び315フィートであってもよい。必要な遅延に基づいて光ファイバの他の長さが選択されてもよく、これは当業者には明白であろう。波長成分のそれぞれを同じ光学検出器で時間的に分離するために、波長成分のそれぞれは光ファイバの異なる長さを通して移動し、これにより、異なる量の遅延を経験する。最終的には、波長成分のそれぞれは異なる時点で光学検出器に届き、各成分が別々に検出されることが可能となる。
ソズマブ(Romosozumab)、ロンタリズマブ(Rontalizumab)、ロベリズマブ(Rovelizumab)、ルプリズマブ(Ruplizumab)、サマリズマブ(Samalizumab)、サリルマブ(Sarilumab)、サツモマブ・ペンデチデ(Satumomab pendetide)、セクキヌマブ(Secukinumab)、セリバンツマブ(Seribantumab)、セトキサキシマブ(Setoxaximab)、セビルマブ(Sevirumab)、SGN−CD19A、SGN−CD33A、シブロツズマブ(Sibrotuzumab)、シファリムマブ(Sifalimumab)、シルツキシマブ(Siltuximab)、シムツズマブ(Simtuzumab)、シプリズマブ(Siplizumab)、シルクマブ(Sirukumab)、ソラネズマブ(Solanezumab)、ソリトマブ(Solitomab)、ソネプシズマブ(Sonepcizumab)、ソンツズマブ(Sontuzumab)、スタムルマブ(Stamulumab)、スレソマブ(Sulesomab)、スビズマブ(Suvizumab)、タバルマブ(Tabalumab)、タカツズマブ・テトラキセタン(Tacatuzumab tetraxetan)、タドシズマブ(Tadocizumab)、タリズマブ(Talizumab)、タネズマブ(Tanezumab)、タプリツモマブ・パプトクス(Taplitumomab paptox)、テフィバズマブ(Tefibazumab)、テリモマブ・アリトクス(Telimomab aritox)、テナツモマブ(Tenatumomab)、テネリキシマブ(Teneliximab)、テプリズマブ(Teplizumab)、テプロツムマブ(Teprotumumab)、TGN1412、チシリムマブ(トレメリムマブ)(Ticilimumab(tremelimumab))、チガツズマブ(Tigatuzumab)、チルドラキズマブ(Tildrakizumab)、TNX−650、トシリズマブ(アトリズマブ)(Tocilizumab(atlizumab))、トラリズマブ(Toralizumab)、トシツモマブ(Tositumomab)、トベツマブ(Tovetumab)、トラロキヌマブ(Tralokinumab)、トラスツズマブ(Trastuzumab)、TRBS07、トレガリズマブ(Tregalizumab)、トレメリムマブ(Tremelimumab)、ツコツズマブ・セルモロイキン(Tucotuzumab celmoleukin)、ツビルマブ(Tuvirumab)、ウブリツキシマブ(Ublituximab)、ウレルマブ(Urelumab)、ウルトキサズマブ(Urtoxazumab)、ウステキヌマブ(Ustekinumab)、バンチクツマブ(Vantictumab)、バパリキシマブ(Vapaliximab)、バテリズマブ(Vatelizumab)、ベドリズマブ(Vedolizumab)、ベルツズマブ(Veltuzumab)、ベパリモマブ(Vepalimomab)、ベセンクマブ(Vesencumab)、ビシリズマブ(Visilizumab)、ボロシキシマブ(Volociximab)、ボルセツズマブ・マフォドチン(Vorsetuzumab mafodotin)、ボツムマブ(Votumumab)、ザルツムマブ(Zalutumumab)、ザノリムマブ(Zanolimumab)、ザツキシマブ(Zatuximab)、ジラリムマブ(Ziralimumab)、ゾリモマブ・アリトクス(Zolimomab aritox)を含むがこれらに限定されない。本明細書で説明されている様に、抗体は、標識される又は標識されない場合がある。いくつかの実施形態では、標識は蛍光標識である。治療薬を標識するために本明細書で説明されるシステム、装置、及び方法と共に用いられ得る蛍光標識の例は、インドシアニングリーン(ICG)、クルクミン、ローダミン(ローダミンB、ローダミン123、ローダミン6G、又はこれらの変種など)、緑色蛍光タンパク質(GFP)、ルシフェリン、フルオレセイン、量子ドット、又はこれらの組み合わせを含むがこれらに限定されない。
励起波長とデマクサの波長分割ビーム分割装置との組み合わせに基づいて、種々の分子の蛍光が分析される場合がある(図4)。例えば、波長350nmでのサンプルの励起とデマクサの適切な波長分割ビーム分割装置により、限定はされないがPLG−GAD(ピリドキサル−5'−リン酸(PLP)グルタミン酸デカルボキシラーゼ(GAD))、結合NADH、及び遊離NADHを含む生体分子の蛍光が分析される場合がある。すなわち、波長440nmでのサンプルの励起とデマクサの適切な波長分割ビーム分割装置で、FAD(フラビンアデニンジヌクレオチド)、FMN(フラビンモノヌクレオチド)、及びポルフィリンなどの生体分子の蛍光を分析することができる。
細胞代謝の連続モニタリング
本明細書で説明されるシステムは、酸素欠乏、神経保護薬の影響などに対応する代謝状態の変化を判断するべく非常に細かいスケールでのNADHレベルの変化の連続モニタリングを可能にする(図1及び図5)。
損傷後の組織生存性の判定
虚血性脳卒中後の脳の広い面積にわたってNADHレベルを記録することは、酸素の欠如によりショック状態にあるかもしれないがアポトーシスされなかった、したがって救出できる、生存可能な細胞の数の評価を可能にする。これらの細胞は半影帯として知られる領域の大半をなし、卒中処置の重要な目標は、できるだけ多くのニューロンを救出しつつ半影帯のサイズを減らすことである。半影帯領域全体にわたるNADHのモニタリングは、このために設計された種々の介入の効果の評価を可能にする。
血漿中の薬剤/代謝産物レベルを判定するための蛍光の使用
いくつかの抗がん剤は、高い投与量で有毒であり、より低い投与量でそれらの有効性を失う。薬剤が最も効果的である薬剤のこの最適血漿濃度(治療濃度域)は、身長、体重、代謝、及び民族の多様性に起因して患者間で異なる。これらの多様性があるにもかかわらず、現在のところ、薬剤投与量は、患者の体重及び標準化された薬物動態プロファイルに基づいて計算される。血漿薬剤レベルを判定する迅速かつ低価格な方法は、個々の患者の投与量の最適化を可能にする。薬剤の血漿レベルは、蛍光分光法を用いて検出されてもよい。メトトレキサートなどの抗がん剤のうちのいくつかは蛍光特性を有することが知られている。本明細書で、出願人らは、本明細書で説明されるTRLIFSシステムを用いて、寒天(図8)中のメトトレキサート(MTX)の濃度を変化させることが、結果的にMTXの蛍光の対応する変化を生じたことを示した。
腫瘍の検出
レーザ誘起蛍光分光法(LIFS)は、インビボ診断のための有望な新しい付加的な技術を表す。蛍光分光法は、組織内の内因性フルオロフォア(標識なし)を励起し、発光を記録することに関係する。蛍光分光法は、定常状態又は時間分解蛍光分光法の2通りで採用される。時間分解測定は、蛍光強度の減衰を寿命の観点から分解し、したがって、蛍光強度の減衰の基礎となる動態についてのさらなる情報を提供する。時間分解測定はまた、蛍光強度に影響する場合がある組織内因性フルオロフォア(例えば血液)による吸収、光退色、又は任意の他の状態などの因子から独立している。別個の蛍光分子の弛緩動態の差異を反映する蛍光減衰特徴を測定することによって、時間分解測定は、重なるスペクトルを分解する能力を有し、蛍光測定の特異性を向上させる。
Butte, P.V, Fang, Q., Jo, J.A., Yong, W.H., Pikul, B.K., Black, K.L., & Marcu, L.(n.d.).Intraoperative delineation of primary brain tumors using time−resolved fluorescence spectroscopy.Journal of Biomedical Optics, 15(2), 027008.doi:10.1117/1.3374049
Butte, P.V, Pikul, B.K., Hever, A., Yong, W.H., Black, K.L., & Marcu, L.(2005).Diagnosis of meningioma by time−resolved fluorescence spectroscopy.Journal of Biomedical Optics, 10(6), 064026.doi:10.1117/1.2141624
Butte, P.V., Mamelak, A.N., Nuno, M., Bannykh, S.I., Black, K.L., & Marcu, L.(2010).Fluorescence lifetime spectroscopy for guided therapy of brain tumors.NeuroImage, 54, S125-S135.doi:10.1016/j.neuroimage.2010.11.001
Marcu, L., Jo, J.a, Butte, P.V, Yong, W.H., Pikul, B.K., Black, K.L., & Thompson, R.C.(2004).Fluorescence lifetime spectroscopy of glioblastoma multiforme.Photochemistry and Photobiology, 80, 98-103.doi:10.1562/2003−12−09−RA−023.1
Yong, W.H., Butte, P.V, Pikul, B.K., Jo, J.A., Fang, Q., Papaioannou, T., ... Marcu, L.(2006).Distinction of brain tissue, low grade and high grade glioma with time−resolved fluorescence spectroscopy.Frontiers in Bioscience: A Journal and Virtual Library, 11(4), 1255-63.Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16368511
Jo, J.a, Fang, Q., Papaioannou, T., & Marcu, L.(2004).Fast model−free deconvolution of fluorescence decay for analysis of biological systems.Journal of Biomedical Optics, 9(4), 743-52.doi:10.1117/1.1752919
Lakowicz, J.R.(2006).Principles of fluorescence spectroscopy (3rd ed., p.xxvi, 954 p.).New York: Springer.Retrieved from http://www.loc.gov/catdir/enhancements/fy0824/2006920796−b.html
Pogue, B.W., Pitts, J.D., Mycek, M.a, Sloboda, R.D., Wilmot, C.M., Brandsema, J.F., & O'Hara, J.a.(2001).In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy.Photochemistry and Photobiology, 74(6), 817-24.Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11783938
Schneckenburger, H.(1992).Fluorescence decay kinetics and imaging of NAD(P)H and flavins as metabolic indicators.Optical Engineering, 31(7), 1447.doi:10.1117/12.57704
Sun, Y., Phipps, J., Elson, D.S., Stoy, H., Tinling, S., Meier, J., ... Marcu, L.(2009).Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma.Opt Lett, 34(13), 2081-2083.doi:183277 [pii]
Claims (19)
- 励起時の生体サンプルからの蛍光発光を分析することによって生体サンプルを特徴付けるためのシステムであって、
(i)励起ファイバ(ExF)を介して生体サンプルに接続されるレーザ光源であって、前記レーザ光源が、前記生体サンプルに応答蛍光シグナルを生じさせるために前記生体サンプルに所定の波長のレーザパルスを放射するように構成される、前記レーザ光源と、
(ii)前記生体サンプルから前記蛍光シグナルを収集し、前記蛍光シグナルをデマルチプレクサにリレーする、集光ファイバ(CF)と、
(iii)365nm未満、365〜410nm、410〜450nm、450〜500nm、500〜560nm、560〜600nm、及び600nmを超える各スペクトルバンドを得るべく前記CFからの前記蛍光シグナルを所定の波長で分割するように構成されたデマルチプレクサであって、
前記デマルチプレクサは、約500nmの第1の波長分割装置、約560nmの第2の波長分割装置、約600nmの第3の波長分割装置、約410nmの第4の波長分割装置、約450nmの第5の波長分割装置、及び約365nmの第6の波長分割装置を含み、
前記CFからの前記蛍光シグナルが、前記第1の波長分割装置により500nm未満のシグナルと500nmを超えるシグナルとに分割され、前記500nmを超えるシグナルが、前記第2の波長分割装置により500〜560nmのシグナルと560nmを超えるシグナルとに分割され、前記560nmを超えるシグナルが、前記第3の波長分割装置により560〜600nmのシグナルと600nmを超えるシグナルとに分割され、前記500nm未満のシグナルが、前記第4の波長分割装置により410nm未満のシグナルと410〜500nmのシグナルとに分割され、前記410〜500nmのシグナルが、前記第5の波長分割装置により410〜450nmのシグナルと450〜500nmのシグナルとに分割され、前記410nm未満のシグナルが、前記第6の波長分割装置により365nm未満のシグナルと365〜410nmのシグナルとに分割される、前記デマルチプレクサと、
(iv)光遅延装置と
を備える、システム。 - 前記光遅延装置が、前記デマルチプレクサからの前記スペクトルバンドを前記光遅延装置に連結するように適合され、単一のショットで複数の波長を捕捉するように、前記スペクトルバンドが前記光遅延装置を通り、かつ、前記スペクトルバンドが前記光遅延装置を通る際に制御された時間遅延を導入することを可能にする、請求項1に記載のシステム。
- 前記集光ファイバが単一のバンドルを形成する、請求項1に記載のシステム。
- 励起時の生体サンプルからの蛍光シグナルの発光を分析することによって生体サンプルを特徴付けるための方法であって、
(i)生体サンプルに応答蛍光シグナルを生じさせるために前記生体サンプルに所定の波長のレーザパルスを放射することと、
(ii)前記生体サンプルから前記蛍光シグナルを収集することと、
(iii)365nm未満、365〜410nm、410〜450nm、450〜500nm、500〜560nm、560〜600nm、及び600nmを超える各スペクトルバンドを得るべく前記蛍光シグナルを所定の波長で分割することであって、
前記蛍光シグナルが、500nm未満のシグナルと500nmを超えるシグナルとに分割され、前記500nmを超えるシグナルが、500〜560nmのシグナルと560nmを超えるシグナルとに分割され、前記560nmを超えるシグナルが、560〜600nmのシグナルと600nmを超えるシグナルとに分割され、前記500nm未満のシグナルが、410nm未満のシグナルと410〜500nmのシグナルとに分割され、前記410〜500nmのシグナルが、410〜450nmのシグナルと450〜500nmのシグナルとに分割され、前記410nm未満のシグナルが、365nm未満のシグナルと365〜410nmのシグナルとに分割される、前記蛍光シグナルを所定の波長で分割することと、
(iv)時間遅延したスペクトルバンドを生成するために、前記スペクトルバンドを時間遅延機構に通すことと、
(v)時間遅延したスペクトルバンドを得ることと、
(vi)前記時間遅延したスペクトルバンドを処理することと
を含む、方法。 - 前記蛍光シグナルが生体分子によって発光される、請求項4に記載の方法。
- 前記生体分子が、PLP−GAD(ピリドキサル−5'−リン酸(PLP)グルタミン酸デカルボキシラーゼ(GAD))、結合NADH、遊離NADH、フラビンモノヌクレオチド(FMN)リボフラビン、フラビンアデニンジヌクレオチド(FAD)リボフラビン、リポピグメント、内因性ポルフィリン、又はこれらの組み合わせのうちのいずれか1つ以上である、請求項5に記載の方法。
- 請求項4に記載の方法によって生体サンプルの生体分子からの蛍光シグナルの発光を分析することを含む組織生存性を判定するための方法であって、正常サンプルと比較しての前記生体サンプルの蛍光シグナルの増加が、低い組織生存性を示す、方法。
- 請求項4に記載の方法によって蛍光シグナルの発光を分析することを含む、細胞の代謝を連続的にモニタリングするための方法。
- 請求項4に記載の方法によって生体分子からの蛍光シグナルの発光を分析することを含む、血漿中の薬剤レベル又は代謝産物レベルを判定するための方法。
- 前記生体分子がNADHである、請求項9に記載の方法。
- NADHが、遊離型、結合型、又はこれらの組み合わせである、請求項10に記載の方法。
- 前記光遅延装置から受信したシグナルの検出用に構成された光電子増倍管をさらに含む、請求項1に記載のシステム。
- 前記光電子増倍管から受信した前記シグナルのデジタル化用に構成されたデジタイザをさらに含む、請求項12に記載のシステム。
- 前記光電子増倍管から受信した前記シグナルを、前記シグナルが前記デジタイザによりデジタル化される前に増幅するように構成された前置増幅器をさらに含む、請求項13に記載のシステム。
- 前記デジタイザから受信したシグナルの処理及び表示用に構成されたコンピュータシステムをさらに含む、請求項13に記載のシステム。
- 前記時間遅延したスペクトルバンドを処理することが、前記時間遅延したスペクトルバンドを検出することを含む、請求項4に記載の方法。
- 検出したシグナルをデジタル化することをさらに含む、請求項16に記載の方法。
- 前記検出したシグナルを、前記検出したシグナルをデジタル化する前に増幅することをさらに含む、請求項17に記載の方法。
- デジタル化したシグナルをコンピュータシステムによって処理及び表示することをさらに含む、請求項17に記載の方法。
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Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9095414B2 (en) * | 2011-06-24 | 2015-08-04 | The Regents Of The University Of California | Nonlinear optical photodynamic therapy (NLO-PDT) of the cornea |
WO2014168734A1 (en) | 2013-03-15 | 2014-10-16 | Cedars-Sinai Medical Center | Time-resolved laser-induced fluorescence spectroscopy systems and uses thereof |
US9814037B2 (en) * | 2013-06-28 | 2017-11-07 | Intel Corporation | Method for efficient channel estimation and beamforming in FDD system by exploiting uplink-downlink correspondence |
WO2017075176A1 (en) * | 2015-10-30 | 2017-05-04 | Cedars-Sinai Medical Center | Methods and systems for performing tissue classification using multi-channel tr-lifs and multivariate analysis |
EP3436805A4 (en) | 2016-04-01 | 2019-12-11 | Black Light Surgical, Inc. | SYSTEMS, DEVICES AND METHODS FOR TIME-RESOLUTION FLUORESCENCE SPECTROSCOPY |
US11204322B2 (en) * | 2016-06-20 | 2021-12-21 | Plair S.a. | Device and method for detecting and/or characterizing fluid-borne particles |
CN110050183A (zh) | 2016-10-11 | 2019-07-23 | 科克理工学院 | 荧光感测系统 |
CA3057409A1 (en) * | 2017-03-22 | 2018-09-27 | Adiuvo Diagnostics Pvt Ltd | Device and method for detection and classification of pathogens |
CN107677654B (zh) * | 2017-09-15 | 2020-05-05 | 哈尔滨工业大学 | 一种基于lif的氧原子绝对浓度时域/空域分辨的测试方法及装置 |
DE102018129807A1 (de) | 2017-11-24 | 2019-06-27 | Deutsches Zentrum für Luft- und Raumfahrt e.V. | Verfahren und System zur Klassifizierung chemischer und biologischer Stoffe |
CN108507986A (zh) * | 2018-03-17 | 2018-09-07 | 杨佳苗 | 差动共焦分立荧光光谱及荧光寿命探测方法与装置 |
CN108801987B (zh) * | 2018-03-17 | 2021-03-23 | 杨佳苗 | 共焦分立荧光光谱及荧光寿命探测方法与装置 |
CN108844929B (zh) * | 2018-05-14 | 2020-10-30 | 杨佳苗 | 分光瞳差动共焦分立荧光光谱及荧光寿命探测方法与装置 |
CN110487756A (zh) * | 2018-05-14 | 2019-11-22 | 杨佳苗 | 分光瞳分立荧光光谱及荧光寿命探测方法与装置 |
CN108844930B (zh) * | 2018-05-14 | 2020-10-30 | 杨佳苗 | 分光瞳共焦分立荧光光谱及荧光寿命探测方法与装置 |
JP2020071152A (ja) * | 2018-10-31 | 2020-05-07 | ソニー株式会社 | 免疫染色方法、免疫染色システム、および免疫染色キット |
CN114729890A (zh) * | 2019-10-17 | 2022-07-08 | C2感官有限公司 | 用于感测和/或认证的发光成像 |
US11796539B2 (en) | 2019-10-17 | 2023-10-24 | C2Sense, Inc. | Systems and methods for determining a characteristic of an emissive species |
CN111504978B (zh) * | 2020-05-13 | 2021-03-30 | 华中科技大学 | 脉冲型延时色散光谱测量方法和装置及光谱成像方法和装置 |
CN112557362B (zh) * | 2020-12-04 | 2022-08-23 | 厦门大学 | Led光源作为连续波激发光源的同步荧光光谱检测方法 |
US20230026634A1 (en) * | 2021-07-22 | 2023-01-26 | Cilag Gmbh International | Surgical data system and classification |
Family Cites Families (103)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US612459A (en) * | 1898-10-18 | Oscar l | ||
US570190A (en) * | 1896-10-27 | sunderland | ||
US1065608A (en) | 1911-10-24 | 1913-06-24 | Patrick A Hennessy | Concrete mixer and conveyer. |
NL7500951A (nl) * | 1975-01-28 | 1976-07-30 | Akzo Nv | Fluorimetrisch aantonen en bepalen van een gereduceerd co-enzym of derivaat in een waterig systeem. |
US5464013A (en) | 1984-05-25 | 1995-11-07 | Lemelson; Jerome H. | Medical scanning and treatment system and method |
ATE133545T1 (de) * | 1988-12-21 | 1996-02-15 | Massachusetts Inst Technology | Verfahren für laserinduzierte fluoreszenz von gewebe |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US4937457A (en) | 1989-02-10 | 1990-06-26 | Slm Instruments, Inc. | Picosecond multi-harmonic fourier fluorometer |
WO1990009637A1 (en) | 1989-02-13 | 1990-08-23 | Research Corporation Technologies, Inc. | Method and means for parallel frequency acquisition in frequency domain fluorometry |
US5151869A (en) | 1990-02-16 | 1992-09-29 | The Boc Group, Inc. | Frequency domain fluorometry using coherent sampling |
US5196709A (en) | 1991-05-03 | 1993-03-23 | University Of Maryland Systems | Fluorometry method and apparatus using a semiconductor laser diode as a light source |
US5762609A (en) | 1992-09-14 | 1998-06-09 | Sextant Medical Corporation | Device and method for analysis of surgical tissue interventions |
US5462879A (en) | 1993-10-14 | 1995-10-31 | Minnesota Mining And Manufacturing Company | Method of sensing with emission quenching sensors |
US5749830A (en) | 1993-12-03 | 1998-05-12 | Olympus Optical Co., Ltd. | Fluorescent endoscope apparatus |
JPH07222712A (ja) | 1994-02-10 | 1995-08-22 | Olympus Optical Co Ltd | 蛍光内視鏡装置 |
JP3448090B2 (ja) * | 1994-02-16 | 2003-09-16 | 浜松ホトニクス株式会社 | エネルギー移動検出法およびその装置 |
US5701902A (en) * | 1994-09-14 | 1997-12-30 | Cedars-Sinai Medical Center | Spectroscopic burn injury evaluation apparatus and method |
US5697373A (en) | 1995-03-14 | 1997-12-16 | Board Of Regents, The University Of Texas System | Optical method and apparatus for the diagnosis of cervical precancers using raman and fluorescence spectroscopies |
US6258576B1 (en) | 1996-06-19 | 2001-07-10 | Board Of Regents, The University Of Texas System | Diagnostic method and apparatus for cervical squamous intraepithelial lesions in vitro and in vivo using fluorescence spectroscopy |
US5991653A (en) | 1995-03-14 | 1999-11-23 | Board Of Regents, The University Of Texas System | Near-infrared raman spectroscopy for in vitro and in vivo detection of cervical precancers |
JP3980683B2 (ja) * | 1995-08-29 | 2007-09-26 | 仁 岩崎 | 還元型ニコチンアミド補酵素の測定用試薬および測定方法 |
US5769081A (en) | 1996-03-18 | 1998-06-23 | The Research Foundation Of City College Of New York | Method for detecting cancerous tissue using optical spectroscopy and fourier analysis |
US5829448A (en) | 1996-10-30 | 1998-11-03 | Photogen, Inc. | Method for improved selectivity in photo-activation of molecular agents |
US6124597A (en) * | 1997-07-07 | 2000-09-26 | Cedars-Sinai Medical Center | Method and devices for laser induced fluorescence attenuation spectroscopy |
US6051437A (en) | 1998-05-04 | 2000-04-18 | American Research Corporation Of Virginia | Optical chemical sensor based on multilayer self-assembled thin film sensors for aquaculture process control |
AU3970799A (en) | 1998-05-04 | 1999-11-23 | Board Of Regents | Combined fluorescence and reflectance spectroscopy |
AU5429199A (en) | 1998-08-08 | 2000-02-28 | Imperial Cancer Research Technology Limited | Modified green fluorescent protein |
DE19940750A1 (de) * | 1998-08-28 | 2000-06-21 | Febit Ferrarius Biotech Gmbh | Träger für Analytbestimmungsverfahren und Verfahren zur Herstellung des Trägers |
US6246817B1 (en) | 1998-09-01 | 2001-06-12 | Innova Quartz Inc. | Optical fiber with numerical aperture compression |
CA2343401C (en) | 1998-09-11 | 2009-01-27 | Spectrx, Inc. | Multi-modal optical tissue diagnostic system |
WO2000036973A1 (en) | 1998-12-23 | 2000-06-29 | Medispectra, Inc. | Optical methods and systems for cervical screening |
US6272376B1 (en) | 1999-01-22 | 2001-08-07 | Cedars-Sinai Medical Center | Time-resolved, laser-induced fluorescence for the characterization of organic material |
US6097485A (en) * | 1999-03-08 | 2000-08-01 | Integrated Waveguides, Inc. | Microchip optical transport technology for use in a personal flow cytometer |
US6697666B1 (en) | 1999-06-22 | 2004-02-24 | Board Of Regents, The University Of Texas System | Apparatus for the characterization of tissue of epithelial lined viscus |
WO2001008552A1 (en) | 1999-08-03 | 2001-02-08 | Biophysica, Llc | Spectroscopic systems and methods for detecting tissue properties |
US7904139B2 (en) | 1999-08-26 | 2011-03-08 | Non-Invasive Technology Inc. | Optical examination of biological tissue using non-contact irradiation and detection |
US7260248B2 (en) | 1999-12-15 | 2007-08-21 | Medispectra, Inc. | Image processing using measures of similarity |
GR1004180B (el) | 2000-03-28 | 2003-03-11 | ����������� ����� ��������� (����) | Μεθοδος και συστημα χαρακτηρισμου και χαρτογραφησης αλλοιωσεων των ιστων |
WO2001082786A2 (en) | 2000-05-03 | 2001-11-08 | Flock Stephen T | Optical imaging of subsurface anatomical structures and biomolecules |
EP2325294B1 (en) | 2000-06-08 | 2016-08-24 | The Regents of The University of California | Visual-servoing optical microscopy |
US7546210B2 (en) | 2000-06-08 | 2009-06-09 | The Regents Of The University Of California | Visual-servoing optical microscopy |
DE60137046D1 (de) | 2000-07-13 | 2009-01-29 | Univ Virginia Commonwealth | Verwendung von ultraviolett, nahultraviolett und nahinfrarot-resonanzrmanspektroskopie und fluoresenzspektoskopie zur gewebeuntersuchung auf schockzustand, kritische krankheiten oder andere krankheitszustände |
US6826424B1 (en) | 2000-12-19 | 2004-11-30 | Haishan Zeng | Methods and apparatus for fluorescence and reflectance imaging and spectroscopy and for contemporaneous measurements of electromagnetic radiation with multiple measuring devices |
US6697652B2 (en) | 2001-01-19 | 2004-02-24 | Massachusetts Institute Of Technology | Fluorescence, reflectance and light scattering spectroscopy for measuring tissue |
US7015484B2 (en) | 2001-04-16 | 2006-03-21 | Dakota Technologies, Inc. | Multi-dimensional fluorescence apparatus and method for rapid and highly sensitive quantitative analysis of mixtures |
US6929779B2 (en) | 2001-06-22 | 2005-08-16 | Biocal Technology, Inc. | Optical detection in bio-separation device using axial radiation output |
GB2382648B (en) * | 2001-12-11 | 2003-11-12 | Amersham Pharm Biotech Uk Ltd | System and method for time correlated multi-photon counting measurements |
US20030136921A1 (en) | 2002-01-23 | 2003-07-24 | Reel Richard T | Methods for fluorescence detection that minimizes undesirable background fluorescence |
US7647092B2 (en) | 2002-04-05 | 2010-01-12 | Massachusetts Institute Of Technology | Systems and methods for spectroscopy of biological tissue |
US20060193905A1 (en) * | 2002-05-14 | 2006-08-31 | University Of Louisville Research Foundation, Inc. | Direct cellular energy delivery system |
US6933154B2 (en) | 2002-07-09 | 2005-08-23 | Medispectra, Inc. | Optimal windows for obtaining optical data for characterization of tissue samples |
US7136518B2 (en) | 2003-04-18 | 2006-11-14 | Medispectra, Inc. | Methods and apparatus for displaying diagnostic data |
US7103401B2 (en) | 2002-07-10 | 2006-09-05 | Medispectra, Inc. | Colonic polyp discrimination by tissue fluorescence and fiberoptic probe |
US6768918B2 (en) | 2002-07-10 | 2004-07-27 | Medispectra, Inc. | Fluorescent fiberoptic probe for tissue health discrimination and method of use thereof |
US7285424B2 (en) * | 2002-08-27 | 2007-10-23 | Kimberly-Clark Worldwide, Inc. | Membrane-based assay devices |
US6897954B2 (en) * | 2002-12-20 | 2005-05-24 | Becton, Dickinson And Company | Instrument setup system for a fluorescence analyzer |
US7192783B2 (en) | 2003-02-05 | 2007-03-20 | Research Foundation Of The City University Of New York | Stokes shift emission spectroscopy for detection of disease and physiological state of specimen |
JP2004305382A (ja) | 2003-04-04 | 2004-11-04 | Olympus Corp | 特殊光観察システム |
US20040225222A1 (en) | 2003-05-08 | 2004-11-11 | Haishan Zeng | Real-time contemporaneous multimodal imaging and spectroscopy uses thereof |
US7890157B2 (en) | 2003-08-19 | 2011-02-15 | Cedars-Sinai Medical Center | Method for fluorescence lifetime imaging microscopy and spectroscopy |
US20050105791A1 (en) | 2003-10-29 | 2005-05-19 | Lee Ken K. | Surface inspection method |
WO2006015251A2 (en) | 2004-07-29 | 2006-02-09 | The Research Foundation Of State University Of New York | System and method for cross-talk cancellation in a multilane fluorescence detector |
EP1784633B1 (en) | 2004-09-01 | 2011-11-09 | Perkinelmer Singapore PTE Ltd. | A method of analysing a sample and apparatus therefor |
US20060229515A1 (en) | 2004-11-17 | 2006-10-12 | The Regents Of The University Of California | Fiber optic evaluation of tissue modification |
WO2006086382A2 (en) * | 2005-02-08 | 2006-08-17 | Northrop Grumman Corporation | System and methods for use in detecting harmful aerosol particles |
CN101189505B (zh) * | 2005-04-01 | 2011-11-09 | 3M创新有限公司 | 具有可移除光学模块的多重荧光检测装置 |
US7709249B2 (en) * | 2005-04-01 | 2010-05-04 | 3M Innovative Properties Company | Multiplex fluorescence detection device having fiber bundle coupling multiple optical modules to a common detector |
CA2615017C (en) | 2005-07-18 | 2015-06-02 | Andreas Mandelis | Method and apparatus using infrared photothermal radiometry (ptr) and modulated laser luminescence (lum) for diagnostics of defects in teeth |
GB2429521A (en) | 2005-08-18 | 2007-02-28 | E2V Tech | CCD device for time resolved spectroscopy |
US8057408B2 (en) * | 2005-09-22 | 2011-11-15 | The Regents Of The University Of Michigan | Pulsed cavitational ultrasound therapy |
US7692798B2 (en) | 2006-09-15 | 2010-04-06 | Adarza Biosystems, Inc. | Method for biomolecular detection and system thereof |
US7824902B2 (en) | 2006-11-03 | 2010-11-02 | Mark Selker | Optical interface for disposable bioreactors |
US8405827B2 (en) | 2006-11-21 | 2013-03-26 | Ricardo Claps | Time-resolved spectroscopy system and methods for multiple-species analysis in fluorescence and cavity-ringdown applications |
WO2008127434A2 (en) * | 2006-11-28 | 2008-10-23 | The Regents Of The University Of California | Time-resolved and wavelength-resolved spectroscopy for characterizing biological materials |
US20100069720A1 (en) | 2006-11-30 | 2010-03-18 | Newton Laboratories, Inc. | Spectroscopically enhanced imaging |
WO2008095075A1 (en) | 2007-02-01 | 2008-08-07 | Ls Biopath, Inc. | Optical system for identification and characterization of abnormal tissue and cells |
US9226731B2 (en) | 2007-05-21 | 2016-01-05 | The Board Of Regents Of The University Of Texas System | Optically guided needle biopsy system using multi-modal spectroscopy in combination with a transrectal ultrasound probe |
WO2008144760A1 (en) | 2007-05-21 | 2008-11-27 | Board Of Regents, The University Of Texas System | Optical methods to intraoperatively detect positive prostate and kidney cancer margins |
US20090099460A1 (en) | 2007-10-16 | 2009-04-16 | Remicalm Llc | Method and device for the optical spectroscopic identification of cervical cancer |
KR100885927B1 (ko) * | 2007-10-16 | 2009-02-26 | 광주과학기술원 | 형광수명 측정 방법 및 장치 |
AU2008324814B2 (en) * | 2007-11-05 | 2013-05-16 | Solventum Intellectual Properties Company | Identification of tissue for debridement |
US8509879B2 (en) * | 2007-11-06 | 2013-08-13 | The Regents Of The University Of California | Apparatus and method for widefield functional imaging (WiFI) using integrated structured illumination and laser speckle imaging |
US8694266B2 (en) | 2008-06-05 | 2014-04-08 | The Regents Of The University Of Michigan | Multimodal spectroscopic systems and methods for classifying biological tissue |
US20100234684A1 (en) | 2009-03-13 | 2010-09-16 | Blume Jurgen | Multifunctional endoscopic device and methods employing said device |
US8264694B2 (en) | 2009-03-16 | 2012-09-11 | Ut-Battelle, Llc | Quantitative phase-contrast and excitation-emission systems |
JP2011062348A (ja) | 2009-09-17 | 2011-03-31 | Fujifilm Corp | 内視鏡システム |
AU2010339972B2 (en) | 2009-12-15 | 2015-04-30 | Emory University | System and method for providing real-time anatomical guidance in a diagnostic or therapeutic procedure |
US20130076861A1 (en) * | 2010-01-21 | 2013-03-28 | Shmuel Sternklar | Method and apparatus for probing an object, medium or optical path using noisy light |
JP5704827B2 (ja) | 2010-03-19 | 2015-04-22 | オリンパス株式会社 | 蛍光観察装置 |
WO2012002886A1 (en) | 2010-06-28 | 2012-01-05 | Ge Healthcare Bio-Sciences Corp | Confocal fluorescence lifetime imaging system |
US9662047B2 (en) | 2010-08-05 | 2017-05-30 | Massachusetts Institute Of Technology | Portable raman diagnostic system |
WO2012048063A2 (en) * | 2010-10-06 | 2012-04-12 | Emd Millipore Corporation | Cyanine compounds, conjugates and method of use |
US20130015370A1 (en) * | 2011-07-15 | 2013-01-17 | Huron Technologies International In | Confocal fluorescence slide scanner with parallel detection |
CN102525481B (zh) | 2011-12-14 | 2014-03-19 | 山东大学 | 一种基于近红外光谱的人体内酒精含量检测方法及系统 |
EP2820398B1 (en) | 2012-03-02 | 2018-10-24 | The Regents of The University of California | Apparatus for time-resolved fluorescence imaging and pulse shaping |
US10376148B2 (en) | 2012-12-05 | 2019-08-13 | Accuvein, Inc. | System and method for laser imaging and ablation of cancer cells using fluorescence |
WO2014168734A1 (en) * | 2013-03-15 | 2014-10-16 | Cedars-Sinai Medical Center | Time-resolved laser-induced fluorescence spectroscopy systems and uses thereof |
US20140273181A1 (en) | 2013-03-15 | 2014-09-18 | Biofire Diagnostics, Inc. | Compact optical system for substantially simultaneous monitoring of samples in a sample array |
US20170238807A9 (en) | 2013-03-15 | 2017-08-24 | LX Medical, Inc. | Tissue imaging and image guidance in luminal anatomic structures and body cavities |
US10362983B2 (en) | 2014-05-12 | 2019-07-30 | Robert R. Alfano | Near infrared photonic prostatoscopy analyzer |
WO2017075176A1 (en) | 2015-10-30 | 2017-05-04 | Cedars-Sinai Medical Center | Methods and systems for performing tissue classification using multi-channel tr-lifs and multivariate analysis |
EP3436805A4 (en) | 2016-04-01 | 2019-12-11 | Black Light Surgical, Inc. | SYSTEMS, DEVICES AND METHODS FOR TIME-RESOLUTION FLUORESCENCE SPECTROSCOPY |
TW201737864A (zh) | 2016-04-08 | 2017-11-01 | 美國錫安山醫學中心 | 使用時間分辨螢光光譜法以及單極和雙極皮質和皮質下刺激器與時間分辨螢光光譜法的組合的組織分類方法 |
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