この研究は、NSERC、カナダによって資金を供給された。

<ol>
	<li>Mairhofer, J., Roppert, K., Ertl, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidic+Systems+for+Pathogen+Sensing.">Microfluidic Systems for Pathogen Sensing.</a> A Review. Sensors. 9, 4804-4823 (2009).</li><li>Jokerst, J. J., Emory, J. M., Henry, C. 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M., Kulkarni, R. 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M., Oveys, H., Fan, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liquid-core+optical+ring-resonator+sensors.">Liquid-core optical ring-resonator sensors.</a> Optics Letters. 9, 1319-1321 (2006).</li><li>Rodriguez, J. R., Bianucci, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Whispering+gallery+modes+in+hollow+cylindrical+microcavities+containing+silicon+nanocrystals.">Whispering gallery modes in hollow cylindrical microcavities containing silicon nanocrystals.</a> Applied Physics Letters. 92, 131119 (2008).</li><li>Bianucci, P., Rodriguez, J. 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K., Zamora, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Refractometric+sensing+with+fluorescent-core+microcavities.">Refractometric sensing with fluorescent-core microcavities.</a> Optics Express. 19, 21540-21551 (2011).</li><li>Teraoka, I., Arnold, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhancing+Sensitivity+of+a+Whispering+Gallery+Mode+Microsphere+Sensor+by+a+High-Refractive+Index+Surface.">Enhancing Sensitivity of a Whispering Gallery Mode Microsphere Sensor by a High-Refractive Index Surface.</a> Layer. J. Opt. Soc. Am. B. 23, 1434-1441 (2006).</li><li>Huang, G., Bolanos Quinones, V. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rolled-up+optical+microcavities+with+subwavelength+wall+thicknesses+for+enhanced+liquid+sensing+applications.">Rolled-up optical microcavities with subwavelength wall thicknesses for enhanced liquid sensing applications.</a> ACS Nano. 4, 3123-3130 (2010).</li><li>Fan, X. D., White, I. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overview+of+novel+integrated+optical+ring+resonator+bio/chemical+sensors.">Overview of novel integrated optical ring resonator bio/chemical sensors.</a> Proceedings of the Society of Photo-Optical Instrumentation Engineers (SPIE). 6452, M4520-M4520 (2007).</li><li>White, I. 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M., Fan, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+opto-fluidic+ring+resonator+biosensor+for+the+detection+of+organophosphorus+pesticides.">An opto-fluidic ring resonator biosensor for the detection of organophosphorus pesticides.</a> Sensors and Actuators B: Chemical. 133, 105-112 (2008).</li><li>Zhu, H., Dale, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+and+Label-Free+Detection+of+Breast+Cancer+Biomarker+CA15-3+in+Clinical+Human+Serum+Samples+with+Optofluidic+Ring+Resonator+Sensors.">Rapid and Label-Free Detection of Breast Cancer Biomarker CA15-3 in Clinical Human Serum Samples with Optofluidic Ring Resonator Sensors.</a> Anal. 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我々は、開示することは何もない。

蛍光コアマイクロキャビティrefractometricセンサとして使用することができる。マイクロ流体センサー、マイクロチューブに比べ22として作用することができる&quot;ロールアップ&quot;マイクロチューブの隔離された例がありますが、それらを簡単に分析して取り扱うとインターフェイスへの単純されているので、毛細血管は、マイクロ流体セットアップに統合し、かなり実用的な利点を持っていることが容易になりますセットアップ。従来のフーリエ解析の手法を用いて、分光システムのピッチよりも小さい少なくとも一桁アール波長シフトを検出することができる。また、このメソッドは、センサーグラム型の測定システムへの統合を可能にします。 これらFCMSは主に液体コア光リング共振器（LCORRs）と競合する。23,24,25 LCORRSは加熱と引っ張って、内側のキャピラリー表面、または加熱し、インフレを溶解するためにチャネルにHFをポンピングすることによって間伐されたガラスキャピラリーアール加圧ガス図26のように毛細管チャネルへ延びるエバネッセント尾を持つWGMsをサポートするために必要なマイクロメートルの薄い壁と毛細血管でこれらの治療結果。 LCORRバイオセンサーは、異なる標的分析物を検出するための様々な実証されている。27,28,29,30 FCMSはLCORRsと比較して、いくつかの明確な利点と制限があります。両方のデバイスは、毛細管チャネルを介して検体の流れに頼っています。両方をシリカ化学に基づいており、同様の方法を用いて官能化することができる。しかしLCORRの分解能と検出限界は、同等のデータ解析メソッドが使用されていると仮定すると、より良いでしょう。 LCORRsがFCMSは従来分光計を使用し、一方、非常に高いサンプリングレートを持っている精度可変レーザ測定に基づいているためです。これは、FCMの検出限界（そして潜在的に感度31）が減少する。我々はこれまでのところ、最高の状態で、検出限界oを達成している10 -6 RIUの値がLCORRsで標準的であるのに対し、F -5約10 RIUは、このテクニックのバリエーションを使用。つの追加の問題は、全体的なシステムコストの分光計の使用にも関する。のSi量子ドットからの蛍光が容易にそのようなオーシャンオプティクスのUSB2000シリーズ（現在〜2000ドルの費用）などのフットプリントの小さい、非冷却ハンドヘルド分光装置で測定することができます。それは顕微鏡の対物レンズと結像分光装置を使用せずに、キャピラリーの小さな領域からWGMスペクトルを得るために簡単でないかもしれませんので、しかし、FCMSでそのような装置の使用は、検討と実験装置のテストが必要になります。 LCORRsは、波長可変レーザと精密ナノ位置決め装置として、 &quot;フィールドに&quot;動作するように高価で困難でもある装置を使用する必要があります。さらに、薄肉キャピラリーは壊れやすいため、取り扱いが困難でもあります。 FCMSは、対照的に、Siなどの青色光源を必要とするmpleダイオードレーザーやLED、および分光器の入射スリット上に蛍光画像を投影する光学系。 FCMは、また、はるかに堅牢薄肉LCORR超えています。のSi量子ドットに比べて、方法はまた、より高い効率と異なるピーク波長を持つことができ、蛍光層の種類に応じて拡張することができます。したがって、好ましいセンサ（LCORR対FCM）の選択は、おそらく意図しているアプリケーションに依存しています。検体の濃度が非常に低いが存在する場合は、LCORRの低い検出限界は有利であろう。使用性、耐久性、実験コストのしやすさが主な関心事である場合、FCMは、分光計、蛍光顕微鏡を使用せずに統合することができれば、より良いオプションかもしれない。明らかに異なる利点と限界を持っていますが、両方のデバイスが潜在的な検体の広い範囲の微小流体解析への応用が期待されています。

わずかなサンプル量を必要とし、ハンドヘルドまたは現場操作可能な機器に組み込むことができ、その化学センシングシステムは、新技術の広い範囲の開発につながる可能性がある。このような技術は、病気や病原体、1環境汚染物質、2および食品安全のためのフィールド診断を含めることができます。3いくつかの技術を積極的に最先端の間で表面プラズモン共鳴（SPR）の物理学に基づいてデバイスと、マイクロ流体化学センサーのために検討されています。 4これらのセンサは、主に大規模な実験装置などが、今では多くの特定の生体分子を検出することが可能であり、商業的な成功を達成している。5 近年、光マイクロキャビティは、SPRベースのシステムと競合する上昇している。マイクロキャビティは、単一のウイルス6そしておそらく単一生体分子を検出するための実証された能力で、驚くほど敏感になることができます<s（後者は、質量検出限界は9小であることは疑う余地がありませんしかし、8、いくつかの議論の対象のまま）7&gt;まで。マイクロキャビティにおいて、検出機構は共振の電界プロファイル内の分析物の存在に起因する光学共振の変化に依存しています。一般に、与えられた検体は、中心周波数、可視性、または線幅での変化に対する共振が発生します。 SPRのシステムと同様に、マイクロキャビティは非特異refractometricセンサーとして、あるいは特定の分析のために官能化されたバイオセンサーとして機能することができます。 円形断面（ 例えばマイクロスフェア、ディスクまたはシリンダー）を有する誘電体微細ウィスパリングギャラリーモード、またはWGMsとして知られる電磁共鳴によって特徴付けられ、類似した音響効果のレイリー卿の調査にまで遡る用語。基本的に10、光WGM波が円形断面sをcircumnavigatesときに発生します内部全反射し、位相で、その出発点に戻りによってECTION。シリカ微小球の電磁共鳴の例を図1aに示されている。この共鳴は、赤道付近のフィット53波長（L = 53）が示されているそのうちのいくつかだけの合計ながら、半径方向に最大1（n = 1）とすることを特徴とする。電界強度のエバネッセント部分が球体の境界の外培地内に延び、従って、マイクロスフェアWGMは外部媒体を感知することができる。 毛細血管はWGMベースのセンサの特に興味深い例です。毛細血管では、円筒形WGMsは球の場合と同様、円形断面の周囲に形成することができます。毛細血管壁が非常に薄い場合には、電磁界の一部は、毛細管チャネル（ 図1b）に延びている。このように、キャピラリーはチャネル内に注入検体のためのマイクロ流体センサとすることができる。これはbです共振液体コア光リングの動作ASIS（LCORR）が11 LCORRsはWGMsを調べるために精密な同調可能レーザ光 ​​源からの光のエバネッセント結合に依存しています。 LCORRの重要な側面は、毛細血管壁がそのモードのサンプルは、チャネルの中程度確保するために（〜1μm）を薄くしなければならないということです。これは、それらの製造上のいくつかの困難を配置し、それらを機械的に脆弱であることが原因。 私たちの仕事では、我々は、蛍光コアマイクロキャビティ（FCM）を呼び出す別の構造を開発しました。12,13 FCMを形成するために、我々のコート高屈折フルオロフォア（具体的には、の層で毛細血管のチャネル壁酸化物が埋め込まれたシリコン量子ドット）。フィルムの高屈折することにより、WGMs（ 図1c）を構築し、放出される放射線を閉じ込めるために必要です。 LCORRとは対照的に、FCMで、モードが発せられた蛍光スペクトルに鋭い最大値として表示されます。の厚さフィルムは非常に重要であり、それが厚すぎるWGMは毛管チャネル媒体をサンプリングしない、それが薄すぎると光閉じ込めが失われ、WGMsが弱くなっています。したがって、FCMの製造は、入念な準備を必要とする困難なプロセスです。これは、現在の論文の主要なトピックである。

<table border="1"><tbody><tr><td> 材料の表 </td><td>会社</td><td>カタログ＃ </td><td>注釈</td></tr><tr><td>シリカマイクロキャピラリー</td><td></td><td></td><td></td></tr><tr><td>柔軟なマイクロボアチューブ</td><td></td><td></td><td>ポリエチレン、タイゴンなど</td></tr><tr><td>接着剤</td><td>マスコット、ノーランドNOA </td><td></td><td></td></tr><tr><td> HSQはMIBKに溶解</td><td></td><td></td><td> 例えば 。、FOX-15 </td></tr><tr><td>メタノール</td><td></td><td></td><td></td></tr><tr><td>エタノール</td><td></td><td></td><td></td></tr><tr><td>蒸留水</td><td></td><td></td><td></td></tr></tbody></table>使用される材料の表1。一覧。

synthesis and operation of fluorescent-core microcavities for refractometric sensing

本稿では、マイクロ流体解析セットアップで動作することができ、蛍光コアマイクロキャビティベースのセンサについて説明します。これらの構造は、従来のマイクロキャピラリーのチャネル表面上の蛍光量子ドット（QD）コーティングの形成に基づいています。シリコン量子ドットは、立法上、多くの国で物質を制御されているII-VI族およびII-VI族化合物の量子ドットに比べて、彼らのせいで無視できる毒性の一部には、このアプリケーションのために特に魅力的である。アンサンブルの発光スペクトルは、毛細血管の機能膜内に捕捉された光の電磁共鳴に対応する蛍光スペクトルに鋭い、狭いピークのセットのチャネル壁上のSi量子ドットのフィルム広範かつ特徴のないですが。これらの共鳴のピーク波長はこのように量子ドットは、検体と物理的に接触したことがないているrefractometricセンサーとして機能するようにデバイスを可能にして、外部媒体に敏感です。実験的蛍光コアマイクロキャピラリーの作製に関連付けられたメソッドは、同様の分析方法として、詳細に説明します。最後に、比較は、マイクロ流体センシング機能の面では、これらの構造を、より広く調査し、液体コア光リング共振器との間で行われます。

キャピラリー製造手順で小さな偏差は、サンプル成功率の大きな変化につながることができます。 図5（広告）では、私たちは失敗した毛細血管の代表例と同様に成功したものを示しています。一般的に、成功したサンプルの視覚的な表示は、毛細血管壁や特徴のない内装で高い強度と組み合わせた赤色蛍光である。蛍光スペクトルはまた、明らかに成功と失敗（ 図5e）との差を示します。良いサンプルは、スペクトル内の明確に定義された（可視≈0.5）WGM振動を示すべきである。 セットアップは、検体は毛細管チャネル（ 図6a）に圧送されるごとに継続してスペクトルを取るようにプログラムすることができます。上記のテクニックを使用すると、データ解析が異なる検体をキャピラリー内に注入されるようにシフトすべきすべてのWGMスペクトル上のバッチジョブとして実行することができます。ここでは、水、メタノールなどの連続的な時系列（ つまりセンサーグラム ）の結果を示し、最後にエタノールをチャンネル内に順次ポンピングされる。結果はこのような単純な分析であっても満足できると考えられていたので、唯一のメインフーリエ成分が、（ 図6b）で、このような場合に選択されました。エラーバーは、最初の100個の測定値（チャンネル内の水を含む）のピーク位置の1つの標準偏差を表す。 これらのデバイスのセンサー動作（単一の静的な測定とは対照的に、 すなわち連続的な時系列）が分析の潜在的に興味深い機能が欠けて回避します。例えば、私たちは、純粋な成分よりも高い屈折率を持つ検体を示す水とメタノールとWGMシフトデータで &quot;バンプ&quot;を参照してください。実際には、水-メタノール混合物は、純粋な相よりも高い屈折率を有することが知られている、小さなマイルの存在を示唆している19ふたつの解の間の興地域。測定をバイオセンシングのために、私たちはセンサーグラムの測定は、検体の結合の性質と特異性を決定するために重要になることを期待しています。 図6cに、我々はまた、ピーク位置の不確実性は、分光器の110 pmのピッチよりもかなり小さいです〜午後10時、であることがわかります。この改善は、ので、ここで検出することができ、データ解析法の達成可能な分光計のピッチよりも小さい大きさの順にシフト。 最後に、キャピラリーの平均感度は、対応する検体の屈折率の範囲で3つのソリューションのためのネットシフト、から入手することができます。これは主に膜厚と屈折率に依存します。後者は同様の方法を用いて調製し平らなフィルム上のエリプソメトリーの測定値から、約1.67であることが知られている。30μmの内径、理論上の最大感度を得るために20を計算することができる文献で ​​開発された摂動論的アプローチを用いて、図21には 、代わりに球状のものの円筒状のソリューションを使用します。この方法では、1.33、（N、L）の最大感度=（1、190）、λ= 780 nm付近にモードのチャンネルインデックスに対して25.7 NM / 265nmの膜厚にRIUに等しくなります。実験の平均感度はフィルムの厚さが最適であることを示し、この波長域では16.0 NM / RIUです。 <img src="/files/ftp_upload/50256/50256fig1.jpg" alt="図1"/> ミクロスフェアのウィスパリングギャラリーモード（）、LCORR（b）、およびFCM（c）の図1電場振幅。後者の2つのケースにおいて、検体は、チャネル内にある、マイクロスフェアのために、検体は外であるため、独立したチャンバーを必要とします。角度の順序は、52 53である間ラジアルモードの順序は、1ですND 65、それぞれ。 <img src="/files/ftp_upload/50256/50256fig2.jpg" alt="図2"/> 図2（a）はキャピラリー人間はFOX-15の溶液に浸漬。それが写真にメニスカスを参照することはできませんが、実験者は、それがチャネルを上昇観察することができます（b）の予備的な分析のための顕微鏡のステージ上で最後の毛細血管のセット。 445 nmのレーザーは左端の毛細血管の中心付近の事件であり、赤い輝きは、Si量子ドットの蛍光である。これは、ガラスキャピラリー壁内に導波に起因し、キャピラリーの終わりに特に強烈な表示されます（c）に成功した、マイクロ流体解析セットアップで開催されたキャピラリー。マイクロポンプ（図示せず）からキャピラリーに注入された流体は、チャネルを介して、右から左へ流れ、処分のために別のチューブに入ります。 図3代表的なWGMスペクトル。上部蛍光イメージは対応する2Dスペクトル画像と一緒に、分光器の入射スリットの位置を示しています。抽出された最後の1Dスペクトルは箱入りの地域からのものである。 <img src="/files/ftp_upload/50256/50256fig4.jpg" alt="図4"/> 図4単一モードがキャピラリWGMスペクトルから抽出され、純粋なローレンツ（式1;赤線）に適合。と傾斜ローレンツ（式2、青線）。後者は明らかに良いフィット、ピークフィッティングを提供していますが低い検出限界を達成するために必要に応じて、一般的には非常に小さなスペクトルシフトを識別するための最良の選択肢ではありません。 <img src="/files/ftp_upload/50256/50256fig5.jpg" alt="図5"/> 図5。 <strong<html> &gt;（広告）が失敗したの蛍光画像のセットと、成功したFCMを示す（）：。ない発光、この毛細血管が正しく記入されなかったか溶液が完全に蒸発させた毛管チャネル（b）において、黄橙色蛍光。ここでは、蛍光領域は、毛細血管の壁の上ではなく中央にありません。一部のサンプルでは、フィルムは、チャネルの中央に縮むように見えます（c）強い赤色蛍光を示していますが、スペクトルにWGMsを欠いている。いくつかの凹凸が膜構造で観察されています（d）の良いWGMsで成功キャピラリーだった。成功した映画の一つの署名がチャンネルの均一性と不規則な機能の欠如である。対応する蛍光スペクトルは、（e）に示されています。 256/50256fig6highres.jpg &quot;/&gt; 図6次に、次いでメタノールとして取らスペクトルの（a）のセット、水、エタノールは毛細血管に送り込まれた。スペクトルは、赤から青に順次撮影された。（b）各蛍光スペクトルのフーリエパワースペクトルを示す。 40 番目の要素は、主に観察可能WGM発振を表しています。対応する位相差式を介して、波長シフトに変換した後、（c）にのみ、このコンポーネントのために採取した、とにプロットされている。 4。エラーバーは60測定用のピークシフトの1つの標準偏差を表す。挿入図は、メタノールからエタノールへの屈折率の範囲で平均感度を示しています。理論的には、波長が増加し、屈折率の増加をシフトして観測されたシフト·データと一致して、したがって、厳密に線形ではありません。

Watch this Scientific Journal Video about Synthesis and Operation of Fluorescent-core Microcavities for Refractometric Sensing at JoVE.com

Synthesis and Operation of Fluorescent-core Microcavities for Refractometric Sensing

蛍光コアマイクロキャビティセンサは、シリカマイクロキャピラリーのチャンネルに高屈折率の量子ドットのコーティングを採用しています。チャネルの中程度を分析するために使用することができるマイクロキャビティ蛍光スペクトルにおける毛管チャネル原因シフトに圧送流体の屈折率の変化。

Refractometricセンシング用蛍光コアマイクロキャビティの合成と操作

This paper discusses  fluorescent core microcavity-based sensors that can operate in a microfluidic  analysis setup. These structures are based on the ...

synthesis-operation-fluorescent-core-microcavities-for-refractometric

Nanyang Technological University

Research

JoVE Journal

Engineering

12.8K ビュー.  University of Alberta. 蛍光コアマイクロキャビティセンサは、シリカマイクロキャピラリーのチャンネルに高屈折率の量子ドットのコーティングを採用しています。チャネルの中程度を分析するために使用することができるマイクロキャビティ蛍光スペクトルにおける毛管チャネル原因シフトに圧送流体の屈折率の変化。

ビデオ: Synthesis and Operation of Fluorescent-core Microcavities for Refractometric Sensing

High-resolution Fiber-optic Microendoscopy for in situ Cellular Imaging

Many biological and clinical studies require the longitudinal study and analysis of morphology and function with cellular level resolution. Traditionally, multiple experiments are run in parallel, with individual samples removed from the study at sequential time points for evaluation by light microscopy. Several intravital techniques have been developed, with confocal, multiphoton, and second harmonic microscopy all demonstrating their ability to be used for imaging in situ 1. With these systems, however, the required infrastructure is complex and expensive, involving scanning laser systems and complex light sources. Here we present a protocol for the design and assembly of a high-resolution microendoscope which can be built in a day using off-the-shelf components for under US$5,000. The platform offers flexibility in terms of image resolution, field-of-view, and operating wavelength, and we describe how these parameters can be easily modified to meet the specific needs of the end user.
We and others have explored the use of the high-resolution microendoscope (HRME) in in vitro cell culture 2-5, in excised 6 and living animal tissues 2,5, and in human tissues in vivo 2,7. Users have reported the use of several different fluorescent contrast agents, including proflavine 2-4, benzoporphyrin-derivative monoacid ring A (BPD-MA) 5, and fluoroscein 6,7, all of which have received full, or investigational approval from the FDA for use in human subjects. High-resolution microendoscopy, in the form described here, may appeal to a wide range of researchers working in the basic and clinical sciences. The technique offers an effective and economical approach which complements traditional benchtop microscopy, by enabling the user to perform high-resolution, longitudinal imaging in situ.

High-resolution Fiber-optic Microendoscopy for in situ Cellular Imaging

In many biological and clinical situations it is advantageous to study cellular processes as they evolve in their native microenvironment. Here we describe the assembly and use of a low-cost fiber-optic microscope which can provide real time imaging in cell culture, animal studies, and clinical patient studies.

高分解能光ファイバMicroendoscopy用その場で細胞イメージング

Many biological and clinical studies require the longitudinal study and analysis of morphology and function with cellular level resolution.  ...

生物工学

Fabrication of Silica Ultra High Quality Factor Microresonators

Whispering gallery resonant cavities confine light in circular orbits at their periphery.1-2 The photon storage lifetime in the cavity, quantified by the quality factor (Q) of the cavity, can be in excess of 500ns for cavities with Q factors above 100 million. As a result of their low material losses, silica microcavities have demonstrated some of the longest photon lifetimes to date1-2. Since a portion of the circulating light extends outside the resonator, these devices can also be used to probe the surroundings. This interaction has enabled numerous experiments in biology, such as single molecule biodetection and antibody-antigen kinetics, as well as discoveries in other fields, such as development of ultra-low-threshold microlasers, characterization of thin films, and cavity quantum electrodynamics studies.3-7
The two primary silica resonant cavity geometries are the microsphere and the microtoroid. Both devices rely on a carbon dioxide laser reflow step to achieve their ultra-high-Q factors (Q&gt;100 million).1-2,8-9 However, there are several notable differences between the two structures. Silica microspheres are free-standing, supported by a single optical fiber, whereas silica microtoroids can be fabricated on a silicon wafer in large arrays using a combination of lithography and etching steps. These differences influence which device is optimal for a given experiment.
Here, we present detailed fabrication protocols for both types of resonant cavities. While the fabrication of microsphere resonant cavities is fairly straightforward, the fabrication of microtoroid resonant cavities requires additional specialized equipment and facilities (cleanroom). Therefore, this additional requirement may also influence which device is selected for a given experiment.
Introduction
An optical resonator efficiently confines light at specific wavelengths, known as the resonant wavelengths of the device. 1-2 The common figure of merit for these optical resonators is the quality factor or Q. This term describes the photon lifetime (&tau;o) within the resonator, which is directly related to the resonator's optical losses. Therefore, an optical resonator with a high Q factor has low optical losses, long photon lifetimes, and very low photon decay rates (1/&tau;o). As a result of the long photon lifetimes, it is possible to build-up extremely large circulating optical field intensities in these devices. This very unique property has allowed these devices to be used as laser sources and integrated biosensors.10
A unique sub-class of resonators is the whispering gallery mode optical microcavity. In these devices, the light is confined in circular orbits at the periphery. Therefore, the field is not completely confined within the device, but evanesces into the environment. Whispering gallery mode optical cavities have demonstrated some of the highest quality factors of any optical resonant cavity to date.9,11 Therefore, these devices are used throughout science and engineering, including in fundamental physics studies and in telecommunications as well as in biodetection experiments. 3-7,12
Optical microcavities can be fabricated from a wide range of materials and in a wide variety of geometries. A few examples include silica and silicon microtoroids, silicon, silicon nitride, and silica microdisks, micropillars, and silica and polymer microrings.13-17 The range in quality factor (Q) varies as dramatically as the geometry. Although both geometry and high Q are important considerations in any field, in many applications, there is far greater leverage in boosting device performance through Q enhancement. Among the numerous options detailed previously, the silica microsphere and the silica microtoroid resonator have achieved some of the highest Q factors to date.1,9 Additionally, as a result of the extremely low optical loss of silica from the visible through the near-IR, both microspheres and microtoroids are able to maintain their Q factors over a wide range of testing wavelengths.18 Finally, because silica is inherently biocompatible, it is routinely used in biodetection experiments.
In addition to high material absorption, there are several other potential loss mechanisms, including surface roughness, radiation loss, and contamination loss.2 Through an optimization of the device size, it is possible to eliminate radiation losses, which arise from poor optical field confinement within the device. Similarly, by storing a device in an appropriately clean environment, contamination of the surface can be minimized. Therefore, in addition to material loss, surface scattering is the primary loss mechanism of concern.2,8
In silica devices, surface scattering is minimized by using a laser reflow technique, which melts the silica through surface tension induced reflow. While spherical optical resonators have been studied for many years, it is only with recent advances in fabrication technologies that researchers been able to fabricate high quality silica optical toroidal microresonators (Q&gt;100 million) on a silicon substrate, thus paving the way for integration with microfluidics.1
The present series of protocols details how to fabricate both silica microsphere and microtoroid resonant cavities. While silica microsphere resonant cavities are well-established, microtoroid resonant cavities were only recently invented.1 As many of the fundamental methods used to fabricate the microsphere are also used in the more complex microtoroid fabrication procedure, by including both in a single protocol it will enable researchers to more easily trouble-shoot their experiments.

We describe the use of a carbon dioxide laser reflow technique to fabricate silica resonant cavities, including free-standing microspheres and on-chip microtoroids. The reflow method removes surface imperfections, allowing long photon lifetimes within both devices. The resulting devices have ultra high quality factors, enabling applications ranging from telecommunications to biodetection.

シリカ超高品質ファクターMicroresonatorsの作製

Whispering gallery resonant cavities confine light in circular orbits at their periphery.1-2 The photon storage lifetime in the cavity, quantified by the ...

工学

Fabrication And Characterization Of Photonic Crystal Slow Light Waveguides And Cavities

Slow light has been one of the hot topics in the photonics community in the past decade, generating great interest both from a fundamental point of view and for its considerable potential for practical applications. Slow light photonic crystal waveguides, in particular, have played a major part and have been successfully employed for delaying optical signals1-4 and the enhancement of both linear5-7 and nonlinear devices.8-11
Photonic crystal cavities achieve similar effects to that of slow light waveguides, but over a reduced band-width. These cavities offer high Q-factor/volume ratio, for the realization of optically12 and electrically13 pumped ultra-low threshold lasers and the enhancement of nonlinear effects.14-16 Furthermore, passive filters17 and modulators18-19 have been demonstrated, exhibiting ultra-narrow line-width, high free-spectral range and record values of low energy consumption.
To attain these exciting results, a robust repeatable fabrication protocol must be developed. In this paper we take an in-depth look at our fabrication protocol which employs electron-beam lithography for the definition of photonic crystal patterns and uses wet and dry etching techniques. Our optimised fabrication recipe results in photonic crystals that do not suffer from vertical asymmetry and exhibit very good edge-wall roughness. We discuss the results of varying the etching parameters and the detrimental effects that they can have on a device, leading to a diagnostic route that can be taken to identify and eliminate similar issues.
The key to evaluating slow light waveguides is the passive characterization of transmission and group index spectra. Various methods have been reported, most notably resolving the Fabry-Perot fringes of the transmission spectrum20-21 and interferometric techniques.22-25 Here, we describe a direct, broadband measurement technique combining spectral interferometry with Fourier transform analysis.26 Our method stands out for its simplicity and power, as we can characterise a bare photonic crystal with access waveguides, without need for on-chip interference components, and the setup only consists of a Mach-Zehnder interferometer, with no need for moving parts and delay scans.
When characterising photonic crystal cavities, techniques involving internal sources21 or external waveguides directly coupled to the cavity27 impact on the performance of the cavity itself, thereby distorting the measurement. Here, we describe a novel and non-intrusive technique that makes use of a cross-polarised probe beam and is known as resonant scattering (RS), where the probe is coupled out-of plane into the cavity through an objective. The technique was first demonstrated by McCutcheon et al.28 and further developed by Galli et al.29

Use of photonic crystal slow light waveguides and cavities has been widely adopted by the photonics community in many differing applications. Therefore fabrication and characterization of these devices are of great interest. This paper outlines our fabrication technique and two optical characterization methods, namely: interferometric (waveguides) and resonant scattering (cavities).

フォトニック結晶スローライト導波路とキャビティの作製と評価

Slow light has been one of the hot topics in the photonics community in the past decade, generating great interest both from a fundamental point of view ...

Lensless Fluorescent Microscopy on a Chip

On-chip lensless imaging in general aims to replace bulky lens-based optical microscopes with simpler and more compact designs, especially for high-throughput screening applications. This emerging technology platform has the potential to eliminate the need for bulky and/or costly optical components through the help of novel theories and digital reconstruction algorithms. Along the same lines, here we demonstrate an on-chip fluorescent microscopy modality that can achieve e.g., &lt;4&mu;m spatial resolution over an ultra-wide field-of-view (FOV) of &gt;0.6-8 cm2 without the use of any lenses, mechanical-scanning or thin-film based interference filters. In this technique, fluorescent excitation is achieved through a prism or hemispherical-glass interface illuminated by an incoherent source. After interacting with the entire object volume, this excitation light is rejected by total-internal-reflection (TIR) process that is occurring at the bottom of the sample micro-fluidic chip. The fluorescent emission from the excited objects is then collected by a fiber-optic faceplate or a taper and is delivered to an optoelectronic sensor array such as a charge-coupled-device (CCD). By using a compressive-sampling based decoding algorithm, the acquired lensfree raw fluorescent images of the sample can be rapidly processed to yield e.g., &lt;4&mu;m resolution over an FOV of &gt;0.6-8 cm2. Moreover, vertically stacked micro-channels that are separated by e.g., 50-100 &mu;m can also be successfully imaged using the same lensfree on-chip microscopy platform, which further increases the overall throughput of this modality. This compact on-chip fluorescent imaging platform, with a rapid compressive decoder behind it, could be rather valuable for high-throughput cytometry, rare-cell research and microarray-analysis.

A lensless on-chip fluorescent microscopy platform is demonstrated that can image fluorescent objects over an ultra-wide field-of-view of e.g., &#62;0.6-8 cm2 with &#60;4&#956;m resolution using a compressive sampling based decoding algorithm. Such a compact and wide-field fluorescent on-chip imaging modality could be valuable for high-throughput cytometry, rare-cell research and microarray-analysis.

チップ上Lensless蛍光顕微鏡

On-chip lensless imaging in general aims to replace bulky lens-based optical microscopes with simpler and more compact designs, especially for ...

Implementation of a Reference Interferometer for Nanodetection

A thermally and mechanically stabilized fiber interferometer suited for examining ultra-high quality factor microcavities is fashioned. After assessing its free spectral range (FSR), the module is put in parallel with a fiber taper-microcavity system and then calibrated through isolating and eliminating random shifts in the laser frequency (i.e. laser jitter noise). To realize the taper-microcavity junction and to maximize the optical power that is transferred to the resonator, a single-mode optical fiber waveguide is pulled. Solutions containing polystyrene nanobeads are then prepared and flown to the microcavity in order to demonstrate the system&#8217;s ability to sense binding to the surface of the microcavity. Data is post-processed via adaptive curve fitting, which allows for high-resolution measurements of the quality factor as well as the plotting of time-dependent parameters, such as resonant wavelength and split frequency shifts. By carefully inspecting steps in the time-domain response and shifting in the frequency-domain response, this instrument can quantify discrete binding events.

A reference interferometer technique, which is designed to remove undesirable laser jitter noise for nanodetection, is utilized for probing an ultra-high quality factor microcavity. Instructions for assembly, setup, and data acquisition are provided, alongside the measurement process for specifying the cavity quality factor.

Nanodetectionのリファレンス干渉計の実装

A thermally and mechanically stabilized fiber interferometer suited for examining ultra-high quality factor microcavities is fashioned. After assessing ...

Fluorescence detection methods for microfluidic droplet platforms

The development of microfluidic platforms for performing chemistry and biology has in large part been driven by a range of potential benefits that accompany system miniaturisation. Advantages include the ability to efficiently process nano- to femoto- liter volumes of sample, facile integration of functional components, an intrinsic predisposition towards large-scale multiplexing, enhanced analytical throughput, improved control and reduced instrumental footprints.1
In recent years much interest has focussed on the development of droplet-based (or segmented flow) microfluidic systems and their potential as platforms in high-throughput experimentation.2-4 Here water-in-oil emulsions are made to spontaneously form in microfluidic channels as a result of capillary instabilities between the two immiscible phases. Importantly, microdroplets of precisely defined volumes and compositions can be generated at frequencies of several kHz. Furthermore, by encapsulating reagents of interest within isolated compartments separated by a continuous immiscible phase, both sample cross-talk and dispersion (diffusion- and Taylor-based) can be eliminated, which leads to minimal cross-contamination and the ability to time analytical processes with great accuracy. Additionally, since there is no contact between the contents of the droplets and the channel walls (which are wetted by the continuous phase) absorption and loss of reagents on the channel walls is prevented.
Once droplets of this kind have been generated and processed, it is necessary to extract the required analytical information. In this respect the detection method of choice should be rapid, provide high-sensitivity and low limits of detection, be applicable to a range of molecular species, be non-destructive and be able to be integrated with microfluidic devices in a facile manner. To address this need we have developed a suite of experimental tools and protocols that enable the extraction of large amounts of photophysical information from small-volume environments, and are applicable to the analysis of a wide range of physical, chemical and biological parameters. Herein two examples of these methods are presented and applied to the detection of single cells and the mapping of mixing processes inside picoliter-volume droplets. We report the entire experimental process including microfluidic chip fabrication, the optical setup and the process of droplet generation and detection.

Droplet-based microfluidic platforms are promising candidates for high throughput experimentation since they are able to generate picoliter, self-compartmentalized vessels inexpensively at kHz rates. Through integration with fast, sensitive and high resolution fluorescence spectroscopic methods, the large amounts of information generated within these systems can be efficiently extracted, harnessed and utilized.

マイクロ流体液滴のプラットフォームのための蛍光検出法

The development of microfluidic platforms for performing chemistry and biology has in large part been driven by a range of potential benefits that ...

Resonance Fluorescence of an InGaAs Quantum Dot in a Planar Cavity Using Orthogonal Excitation and Detection

The ability to perform simultaneous resonant excitation and fluorescence detection is important for quantum optical measurements of quantum dots (QDs). Resonant excitation without fluorescence detection &#8211; for example, a differential transmission measurement &#8211; can determine some properties of the emitting system, but does not allow applications or measurements based on the emitted photons. For example, the measurement of photon correlations, observation of the Mollow triplet, and realization of single photon sources all require collection of the fluorescence. Incoherent excitation with fluorescence detection &#8211; for example, above band-gap excitation &#8211; can be used to create single photon sources, but the disturbance of the environment due to the excitation reduces the indistinguishability of the photons. Single photon sources based on QDs will have to be resonantly excited to have high photon indistinguishability, and simultaneous collection of the photons will be necessary to make use of them. We demonstrate a method to resonantly excite a single QD embedded in a planar cavity by coupling the excitation beam into this cavity from the cleaved face of the sample while collecting the fluorescence along the sample&#39;s surface normal direction. By carefully matching the excitation beam to the waveguide mode of the cavity, the excitation light can couple into the cavity and interact with the QD. The scattered photons can couple to the Fabry-Perot mode of the cavity and escape in the surface normal direction. This method allows complete freedom in the detection polarization, but the excitation polarization is restricted by the propagation direction of the excitation beam. The fluorescence from the wetting layer provides a guide to align the collection path with respect to the excitation beam. The orthogonality of the excitation and detection modes enables resonant excitation of a single QD with negligible laser scattering background.

Resonant excitation of a single self-assembled quantum dot can be achieved using an excitation mode orthogonal to the fluorescence collection mode. We demonstrate a method using the waveguide and Fabry-Perot modes of a planar microcavity surrounding the quantum dots. The method allows complete freedom in the detection polarization.

直交の励起と検出を用いた平面キャビティ内 InGaAs 量子ドットの共鳴蛍光

The ability to perform simultaneous resonant excitation and fluorescence detection is important for quantum optical measurements of quantum dots (QDs). ...

High-Throughput Total Internal Reflection Fluorescence and Direct Stochastic Optical Reconstruction Microscopy Using a Photonic Chip

Total internal reflection fluorescence (TIRF) is commonly used in single molecule localization based super-resolution microscopy as it gives enhanced contrast due to optical sectioning. The conventional approach is to use high numerical aperture microscope TIRF objectives for both excitation and collection, severely limiting the field of view and throughput. We present a novel approach to generating TIRF excitation for imaging with optical waveguides, called chip-based nanoscopy. The aim of this protocol is to demonstrate how chip-based imaging is performed in an already built setup. The main advantage of chip-based nanoscopy is that the excitation and collection pathways are decoupled. Imaging can then be done with a low magnification lens, resulting in large field of view TIRF images, at the price of a small reduction in resolution. Liver sinusoidal endothelial cells (LSECs) were imaged using direct stochastic optical reconstruction microscopy (dSTORM), showing a resolution comparable to traditional super-resolution microscopes. In addition, we demonstrate the high-throughput capabilities by imaging a 500 &#181;m x 500 &#181;m region with a low magnification lens, providing a resolution of 76 nm. Through its compact character, chip-based imaging can be retrofitted into most common microscopes and can be combined with other on-chip optical techniques, such as on-chip sensing, spectroscopy, optical trapping, etc. The technique is thus ideally suited for high throughput 2D super-resolution imaging, but also offers great opportunities for multi-modal analysis.

Chip-based super-resolution optical microscopy is a novel approach to fluorescence microscopy and offers advantages in cost effectiveness and throughput. Here, the protocols for chip preparation and imaging are shown for TIRF microscopy and localization-based super-resolution microscopy.

フォトニックチップを用いたハイスループット全内部反射蛍光と直接確率光学再構成顕微鏡

Total internal reflection fluorescence (TIRF) is commonly used in single molecule localization based super-resolution microscopy as it gives enhanced ...

生化学

A Modular Microfluidic Technology for Systematic Studies of Colloidal Semiconductor Nanocrystals

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light emitting diodes (LEDs) and photovoltaics (PVs). Among this material group, inorganic/organic perovskites have demonstrated significant improvement and potential towards high-efficiency, low-cost PV fabrication due to their high charge carrier mobilities and lifetimes. Despite the opportunities for perovskite QDs in large-scale PV and LED applications, the lack of fundamental and comprehensive understanding of their growth pathways has inhibited their adaptation within continuous nanomanufacturing strategies. Traditional flask-based screening approaches are generally expensive, labor-intensive, and imprecise for effectively characterizing the broad parameter space and synthesis variety relevant to colloidal QD reactions. In this work, a fully autonomous microfluidic platform is developed to systematically study the large parameter space associated with the colloidal synthesis of nanocrystals in a continuous flow format. Through the application of a novel translating three-port flow cell and modular reactor extension units, the system may rapidly collect fluorescence and absorption spectra across reactor lengths ranging 3 - 196 cm. The adjustable reactor length not only decouples the residence time from the velocity-dependent mass transfer, it also substantially improves the sampling rates and chemical consumption due to the characterization of 40 unique spectra within a single equilibrated system. Sample rates may reach up to 30,000 unique spectra per day, and the conditions cover 4 orders of magnitude in residence times ranging 100 ms - 17 min. Further applications of this system would substantially improve the rate and precision of the material discovery and screening in future studies. Detailed within this report are the system materials and assembly protocols with a general description of the automated sampling software and offline data processing.

Detailed herein are the operation and assembly protocols of a modular microfluidic screening platform for the systematic characterization of colloidal semiconductor nanocrystal syntheses. Through fully adjustable system arrangements, highly efficient spectra collection may be carried out across 4 orders of magnitude reaction time scales within a mass transfer-controlled sampling space.

コロイド状半導体ナノ結晶の分類学的研究のためのモジュラー マイクロ流体技術

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light ...

Excitation-Scanning Hyperspectral Imaging Microscopy to Efficiently Discriminate Fluorescence Signals

Several techniques rely on detection of fluorescence signals to identify or study phenomena or to elucidate functions. Separation of these fluorescence signals were proven cumbersome until the advent of hyperspectral imaging, in which fluorescence sources can be separated from each other as well as from background signals and autofluorescence (given knowledge of their spectral signatures). However, traditional, emission-scanning hyperspectral imaging suffers from slow acquisition times and low signal-to-noise ratios due to the necessary filtering of both excitation and emission light. It has been previously shown that excitation-scanning hyperspectral imaging reduces the necessary acquisition time while simultaneously increasing the signal-to-noise ratio of acquired data. Using commercially available equipment, this protocol describes how to assemble, calibrate, and use an excitation-scanning hyperspectral imaging microscopy system for separation of signals from several fluorescence sources in a single sample. While highly applicable to microscopic imaging of cells and tissues, this technique may also be useful for any type of experiment utilizing fluorescence in which it is possible to vary excitation wavelengths, including but not limited to: chemical imaging, environmental applications, eye care, food science, forensic science, medical science, and mineralogy.

Spectral imaging has become a reliable solution for identification and separation of multiple fluorescence signals in a single sample and can readily distinguish signals of interest from background or autofluorescence. Excitation-scanning hyperspectral imaging improves on this technique by decreasing the necessary image acquisition time while simultaneously increasing the signal-to-noise ratio.

蛍光信号を効率的に判別する励起走査察ハイパースペクトルイメージング顕微鏡

Several techniques rely on detection of fluorescence signals to identify or study phenomena or to elucidate functions. Separation of these fluorescence ...

Refractometricセンシング用蛍光コアマイクロキャビティの合成と操作

要約

さらに動画を探す

この動画の章

高分解能光ファイバMicroendoscopy用その場で細胞イメージング

シリカ超高品質ファクターMicroresonatorsの作製

フォトニック結晶スローライト導波路とキャビティの作製と評価

チップ上Lensless蛍光顕微鏡

Nanodetectionのリファレンス干渉計の実装

マイクロ流体液滴のプラットフォームのための蛍光検出法

直交の励起と検出を用いた平面キャビティ内 InGaAs 量子ドットの共鳴蛍光

フォトニックチップを用いたハイスループット全内部反射蛍光と直接確率光学再構成顕微鏡

コロイド状半導体ナノ結晶の分類学的研究のためのモジュラーマイクロ流体技術

蛍光信号を効率的に判別する励起走査察ハイパースペクトルイメージング顕微鏡

Refractometricセンシング用蛍光コアマイクロキャビティの合成と操作

要約

さらに動画を探す

この動画の章

高分解能光ファイバMicroendoscopy用その場で細胞イメージング

シリカ超高品質ファクターMicroresonatorsの作製

フォトニック結晶スローライト導波路とキャビティの作製と評価

チップ上Lensless蛍光顕微鏡

Nanodetectionのリファレンス干渉計の実装

マイクロ流体液滴のプラットフォームのための蛍光検出法

直交の励起と検出を用いた平面キャビティ内 InGaAs 量子ドットの共鳴蛍光

フォトニックチップを用いたハイスループット全内部反射蛍光と直接確率光学再構成顕微鏡

コロイド状半導体ナノ結晶の分類学的研究のためのモジュラー マイクロ流体技術

蛍光信号を効率的に判別する励起走査察ハイパースペクトルイメージング顕微鏡

コロイド状半導体ナノ結晶の分類学的研究のためのモジュラーマイクロ流体技術