Pallav Kolli、ファビオSettecase、マシューAmans、とUCSFのロバート·テイラー、ペンシルベニア大学のティム·ロバーツ資金源 NIHの国立心臓肺血液研究所（NHLBI）賞（M·ウィルソン）：神経放射線研究·教育財団奨学生賞1R01HL076486アメリカン協会（S. Hetts） 生体イメージングとバイオのNIHの国立研究所（NIBIB）賞（S. Hetts）：1R01EB012031

1。マイクロコイルの作製<ol><li>基板用の市販のマイクロカテーテル（ 例えば 2.3Fラピッド·トランジットコーディス神経血管カテーテル、レインハム、MA）を取得します。 </li><li>カテーテルのサイズが2.3から3.0 Fを全く鉄の成分は、MR-安全であると見なされており、範囲を持っていないことを確認してください</li><li> 1〜2ミリメートル外径絶縁チューブかれ銅シード層が続くチタン接着層をスパッタする。可能な材料としては、ポリイミドやアルミナ（Ortech先進セラミックス、サクラメント、カリフォルニア州）。 </li><li>シプリーのPEPrと-2400（現在の名前Intervia 3D-Pの下ダウケミカルが販売している）を使用して、ポジ型フォトレジスト層を電着。非平面円筒面上に均一なコーティングで電結果。 </li><li>フォトレジストは、所望のコイルフォーム（ 図2A）のパターンのユニークなレーザー直接描画システム（レーザー旋盤、ローレンス·リバモア国立研究所で開発された非商用システム）によって公開されます。これはmodificaですもともとMalba らに記載された技術のる14 </li><li> 35℃で炭酸カリウムの1％溶液で露光されたフォトレジストを開発</li><li>銅は、所望のコイルを形成するために、残りのレジストマスクを介して電気めっきされる。システムは、ソレノイドとヘルムホルツ（競馬場）の銅パターン（ 図2Cおよび2D）の両方を製造することができる。 </li><li>銅電着した後、ホット現像液でレジストを除去。チタン接着層が続く銅シード層を削除します。 </li><li>組み立てを完了し、シュリンクラップを使用してカテーテル先端に絶縁チューブを取り付けます。シュリンクラップ全体のコイル先端を覆っていることを確認します。 図2Eに示すように、多軸カテーテルをアセンブルするには、互いの内部に絶縁チューブ構造を配置します。 </li><li>先端のコイルにマイクロカテーテルと半田の内腔に通した銅線を。 </li><li> 6フィートRJ11電話ケーブルトンを変更して短縮長さはO 3フィート</li><li>マイクロカテーテルの後端ハブから修正された3フィートの電話ジャック伝送路に放出される銅線を接続します。 </li></ol> 2。水槽のセットアップ<ol><li>底から約5cmのプラスチック洗面器の側面の中央に小さな穴をあけます。 </li><li>穴を通して9Fアヴァンティコーディス血管シース（血管内コーディス、マイアミレイクス、フロリダ州）を挿入します。 </li><li>盆地にに延びる4センチメートル-長い作品を残し血管シースの遠位先端をカットします。 </li><li>シースの終わりには、マイクロカテーテルの位置を安定させるために回転止血またはThuoy-ボーストバルブを取り付けます。 </li><li>蒸留水は、装置を完全に水没を確実に洗面器を埋める。 </li><li>血管シースとバルブを介してコイル状の先端でカテーテルを挿入します。 </li><li>測定し、中のバルブから水浴に伸びるマイクロカテーテルの気ままな長さを記録。 </li><li>マイクロで水浴を置き磁石のボアに対してMRスキャナと東洋の磁石内のカテーテルシステム。 </li><li> 2ウェイフォンジャックを使用して25フィートRJ11電話ケーブル伝送路にカテーテルに取り付け修正3フィートの電話ケーブルを接続します。 </li><li>デバイスへの1の電流を供給するようにラムダLPD-422A-FMデュアル安定化電源に25フィートの電話ケーブルのもう一方の端を接続します。 </li><li> 5ガウスラインの外のMRスキャナ室の外導波路と電源を介して送電線を配置します。 </li></ol> 3。血管ファントムのセットアップ<ol><li>ゴムチューブから実験開始までにY字路を有する中空容器ファントムを構築します。 </li><li>ファントム船と背景のコントラストを作成するには、蒸留水でgadopentetateジメグルミン（GdDTPA）（Magnevist、バイエルヘルスケアファーマシューティカルモントビル、ニュージャージー州）の0.​​0102 M溶液と血管ファントムを埋める。 </li><li>のMicroCを組み立てる1.9〜ステップ1.1で概説されているようatheterはシステム。手順2.11から2.9で説明したように電源との位置にカテーテルを接続します。 </li><li>容器開口部の基部にマイクロカテーテルの先端の位置を決めます。 </li><li>磁石のボアに対してMRスキャナと東洋の磁石内にファントムを置きます。 </li></ol> 4。磁気共鳴画像<ol><li> 1.5Tの臨床MRシステム（：;フィリップスAchieva、SWリリース2.1、クリーブランド、オハイオ州Syngo B13、エアランゲン、ドイツシーメンスAvanto、SW）との撮像を行う。 </li><li>カテーテル先端の位置を視覚化するために現在の&lt;50ミリアンペアを適用します。 MRI下で、小さな磁気モーメントは、コイルに通電されているに応じて形状を変化させることの明確な成果物を可視化するために、カテーテル先端部で生産される。 </li><li>コイルにラムダデュアル電源から±100 mAの範囲で電流の可変量を適用し、水BA内の先端偏向（ 図3A-3C）を観察する番目のセットアップ。先端のたわみはほぼ瞬時であるため、電流は最大たわみを可視化するために〜1〜2秒のために適用されるだけで済みます。 </li><li>現在の設定金額の連続した​​アプリケーションを繰り返して記録します。 </li><li>同時に血管ファントム（ 図4Aおよび図4B）を介して機械的な発展を可能にする手でカテーテルを押しながら、4.2の手順を繰り返します。所望の血管にカテーテル先端をそらすために分岐点に現在適用されます。手動でカテーテル先端（ 図4C）を押して、分枝血管にカテーテルを進める。反対側の枝の血管分岐と繰り返し（ 図4D）にカテーテルを収納してください。 </li><li> 2Dスナップショットフラッシュシーケンス（TR = 30ミリ秒、TE = 1.4ミリ秒、256 X128の行列とフリップ角〜30℃）を使用して、MR画像を収集。 </li></ol> 5。たわみ測定中に撮影した画像の角度偏向を分析し、測定様々なコンピュータ·アプリケーション（医学のどのデジタル画像と通信（DICOM）ビューア）と水槽実験を行った。

<ol>
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H., 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=Magnetically+directable+remote+guidance+systems,+and+methods+and+use+thereof.">Magnetically directable remote guidance systems, and methods and use thereof.</a> United States Patent. , (2001).</li><li>Roberts, T. P., Hassenzahl, W. V., Hetts, S. W., Arenson, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remote+control+of+catheter+tip+deflection:+an+opportunity+for+interventional+MRI.">Remote control of catheter tip deflection: an opportunity for interventional MRI.</a> Magn. Reson. 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W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remote+control+catheter+navigation:+options+for+guidance+under+MRI.">Remote control catheter navigation: options for guidance under MRI.</a> Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 14, 33 (2012).</li><li>Wilson, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+catheter+manipulation+in+the+interventional+MRI+environment.">Magnetic catheter manipulation in the interventional MRI environment.</a> J. Vasc. Interv. Radiol. , (2013).</li></ol>

博士Hettsはストライカー社から助成金を受け、シルクロード·メディカル社の有給コンサルタントであるた

ここでは、MRスキャナでマイクロカテーテルのたわみのためのプロトコルを記述します。成功のための重要なパラメータは、現在のと偏向角の測定の正確な適用である。偏向角の不正確な測定では、このプロトコルで遭遇する最も可能性のエラーです。水槽実験の間にMR画像でキャプチャ角度は、媒体が磁石のボアに対して配置されることによって向きのわずかな違いにより、実際の値と異な...

そのような脳動脈瘤、虚血性脳卒中、固形腫瘍、アテローム性動脈硬化症および世界1年間100万人以上の患者を対象とした不整脈のようないくつかの主要な病気を治療するための血管系を通してカテーテルナビゲーションのためのツールとして介入医療用X線ガイダンスで行う血管内処置- 5。造影剤を使用することで、血管系を介してナビゲーションが介入の手6によりカテーテルの手動回転と機械的な進歩によって達成される。しかし、多くの血管の曲がりの周りの小さな曲がりくねった血管を通るナビゲーションは、標的部位に到達するまでの時間を長くすることは、ますます困難になる。これは、このような閉塞した血管内の血栓を除去するなどの時間に敏感な手順については、問題が発生します。さらに、長引く手続きは放射線量を増加させ、有害事象は7月11日の可能性を作成します。マネッティ下で行わしかし、血管内処置C共鳴イメージングは​​、ソリューションを提供することがあります。 MRIスキャナの強い均質磁場がリモコン12,13によりカテーテル先端のナビゲーションのために悪用される可能性があります。カテーテル先端に位置するマイクロコイルに印加される電流は、それがMRIスキャナ13（ 図1）の穴と揃うようにトルクが発生し、小さな磁気モーメントを誘発する。電流は個々のコイルにアクティブになっている場合は、カテーテル先端リモコンで一つの平面内に偏向させることができる。カテーテル先端の3コイルに通電している場合は、カテーテル先端のたわみは、3次元で達成することができます。このように、カテーテルの磁気促進ステアリングは手続き時間を短縮し、患者の転帰を改善することができる血管内処置における血管ナビゲーションの速度と有効性を、増加する可能性を秘めている。マイクロコイル先端が血管内カテーテルに印加される電流は、信頼性、制御されたdeflectiを作り出すことができる場合は、この研究では、検討カテーテルナビゲーションの研究の予備試験として、MR-指導の下、アドオン。

<table border="1">
<tbody>
 <tr>
 <td>Name of Reagent/Material</td>
 <td>Company</td>
 <td>Catalog Number</td>
 <td>Comments</td>
 </tr>
 <tr>
 <td>GdDTPA Contrast Media (Magnevist)</td>
 <td>Bayer HealthCare Pharmaceuticals Inc. </td>
 <td>1240340</td>
 <td>McKesson Material Number</td>
 </tr>
 <tr>
 <td>Positive Photoresist</td>
 <td>Shipley</td>
 <td>N/A</td>
 <td>PEPR-2400, Replacement: Dow Chemicals Intervia 3D-P </td>
 </tr>
 <tr>
 <td>Copper Sulfate</td>
 <td>ScienceLab</td>
 <td>SLC3778</td>
 <td>Crystal form</td>
 </tr>
 <tr>
 <td>Sulfuric Acid</td>
 <td>ScienceLab</td>
 <td>SLS1573</td>
 <td>50% w/w solution</td>
 </tr>
 <tr>
 <td>Parrafin Wax</td>
 <td>Carolina</td>
 <td>879190</td>
 <td></td>
 </tr>
 <tr>
 <td>Potassium Carbonate </td>
 <td>Acros Organics</td>
 <td>424081000</td>
 <td></td>
 </tr>
</tbody>
 </table>

magnetically-assisted remote controlled microcatheter tip deflection under magnetic resonance imaging

X線透視誘導血管内処置が困難なカテーテルナビゲーションと潜在的にMRの指導の下、磁気的操作可能なカテーテルを使用して克服することができる電離放射線の使用を含めて、いくつかの重要な制限があります。 この作品の主な目標は、その先端遠隔MRスキャナの磁場を用いて制御することができるマイクロカテーテルを開発することである。このプロトコルは、一貫して制御可能な偏向を生成するマイクロコイル先端がマイクロカテーテルに通電するための手順について説明することを目指しています。 マイクロコイルは、ポリイミド、先端が血管内カテーテルにレーザー旋盤リソグラフィを用いて作製した。 インビトロ試験を定常自由歳差運動（SSFP）シーケンシングを用いて1.5-TのMRシステムの指導の下、水浴及び血管ファントムで行われた。現在、様々な量のMEAを製造するためにマイクロカテーテルのコイルに印加されたsureable先端のたわみや血管ファントムにナビゲートします。 この装置の開発は、今後のテストおよび血管内インターベンMRI環境に革命をする機会のためのプラットフォームを提供します。

上記のプロトコルから、0度と90度の間の偏向角は、結合されたソレノイド及びヘルムホルツコイルマイクロカテーテルシステム（ 図2E）の両方のコイルに同時に供給される電流の50〜300ミリアンペアのアプリケーションから観察されるべきである。正の電流で観察されるような電流極性の反転は正反対の方向にたわみが生じるべきである一方、印加電流の増加は、マイクロカテー...

Watch this Scientific Journal Video about Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging at JoVE.com

Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging

レーザー旋盤リソグラフィ製マイクロコイル先端が血管内マイクロカテーテルに適用されている現在では、さまざまな血管内処置時の脈管構造のナビゲーションの速度と効率を向上させることができ、磁気共鳴（MR）の指導の下で制御可能な偏向を実現することができます。

磁気共鳴イメージング下磁気アシストリモート制御マイクロカテーテルの先端偏向

X-ray fluoroscopy-guided  endovascular procedures have several significant limitations, including  difficult catheter navigation and use of ionizing ...

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12.3K ビュー.  University of California, San Francisco. レーザー旋盤リソグラフィ製マイクロコイル先端が血管内マイクロカテーテルに適用されている現在では、さまざまな血管内処置時の脈管構造のナビゲーションの速度と効率を向上させることができ、磁気共鳴（MR）の指導の下で制御可能な偏向を実現することができます。

ビデオ: Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging

Magnetic Resonance Elastography Methodology for the Evaluation of Tissue Engineered Construct Growth

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use of destructive assessment is not acceptable. A proposed alternative is the use of an imaging process called magnetic resonance elastography. Elastography is a nondestructive method for determining the engineered outcome by measuring local mechanical property values (i.e., complex shear modulus), which are essential markers for identifying the structure and functionality of a tissue. As a noninvasive means for evaluation, the monitoring of engineered constructs with imaging modalities such as magnetic resonance imaging (MRI) has seen increasing interest in the past decade1. For example, the magnetic resonance (MR) techniques of diffusion and relaxometry have been able to characterize the changes in chemical and physical properties during engineered tissue development2. The method proposed in the following protocol uses microscopic magnetic resonance elastography (&mu;MRE) as a noninvasive MR based technique for measuring the mechanical properties of small soft tissues3. MRE is achieved by coupling a sonic mechanical actuator with the tissue of interest and recording the shear wave propagation with an MR scanner4. Recently, &mu;MRE has been applied in tissue engineering to acquire essential growth information that is traditionally measured using destructive mechanical macroscopic techniques5. In the following procedure, elastography is achieved through the imaging of engineered constructs with a modified Hahn spin-echo sequence coupled with a mechanical actuator. As shown in Figure 1, the modified sequence synchronizes image acquisition with the transmission of external shear waves; subsequently, the motion is sensitized through the use of oscillating bipolar pairs. Following collection of images with positive and negative motion sensitization, complex division of the data produce a shear wave image. Then, the image is assessed using an inversion algorithm to generate a shear stiffness map6. The resulting measurements at each voxel have been shown to strongly correlate (R2&gt;0.9914) with data collected using dynamic mechanical analysis7. In this study, elastography is integrated into the tissue development process for monitoring human mesenchymal stem cell (hMSC) differentiation into adipogenic and osteogenic constructs as shown in Figure 2.

The procedure demonstrates the methodology of magnetic resonance elastography for monitoring the engineered outcome of adipose and osteogenic tissue engineered constructs through noninvasive local assessment of the mechanical properties using microscopic magnetic resonance elastography (&mu;MRE).

ティッシュエンジニアーコンストラクトの成長評価のための磁気共鳴エラストグラフィの方法論

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use ...

生物工学

Remote Magnetic Actuation of Micrometric Probes for in situ 3D Mapping of Bacterial Biofilm Physical Properties

Bacterial adhesion and growth on interfaces lead to the formation of three-dimensional heterogeneous structures so-called biofilms. The cells dwelling in these structures are held together by physical interactions mediated by a network of extracellular polymeric substances. Bacterial biofilms impact many human activities and the understanding of their properties is crucial for a better control of their development &#8212; maintenance or eradication &#8212; depending on their adverse or beneficial outcome. This paper describes a novel methodology aiming to measure in situ the local physical properties of the biofilm that had been, until now, examined only from a macroscopic and homogeneous material perspective. The experiment described here&#160;involves introducing magnetic particles into a growing biofilm to seed local probes that can be remotely actuated without disturbing the structural properties of the biofilm. Dedicated magnetic tweezers were developed to exert a defined force on each particle embedded in the biofilm. The setup is mounted on the stage of a microscope to enable the&#160;recording of time-lapse images of the particle-pulling period. The particle trajectories are then extracted from the pulling sequence and the local viscoelastic parameters are derived from each particle displacement curve, thereby providing the 3D-spatial distribution of the parameters. Gaining insights into the biofilm mechanical profile is essential from an engineer&#39;s point of view for biofilm control purposes but also from a fundamental perspective to clarify the relationship between the architectural properties and the specific biology of these structures.

Remote Magnetic Actuation of Micrometric Probes for in situ 3D Mapping of Bacterial Biofilm Physical Properties

This paper shows an original methodology based on the remote actuation of magnetic particles seeded in a bacterial biofilm and the development of dedicated magnetic tweezers to measure in situ the local mechanical properties of the complex living material built by micro-organisms at interfaces.

のためのマイクロメトリックプローブの遠隔磁気作動<em&gt;その場での</em細菌バイオフィルム物性&gt; 3Dマッピング

Bacterial adhesion and growth on interfaces lead to the formation of three-dimensional heterogeneous structures so-called biofilms. The cells dwelling in ...

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e.,&#160;gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.

AN MRI-compatible&#160;custom-designed laser-based heating apparatus has been developed to provide local heating of subcutaneous tumors in order to activate release of agents from thermosensitive liposomes specifically at the tumor region.

磁気共鳴画像誘導による感熱リポソームからのシスプラチンのトリガリリースのためのカスタム設計されたレーザーベースの加熱装置

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of smart soft devices for biomedical applications. Although a number of magnetically-responsive drug delivery systems have demonstrated efficacies through either in vitro proof of concept studies or in vivo preclinical applications, their use in clinical settings is still limited by their insufficient biocompatibility or biodegradability. Additionally, many of the existing platforms rely on sophisticated techniques for their fabrications. We recently demonstrated the fabrication of biodegradable, gelatin-based thermo-responsive microgel by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within a three-dimensional gelatin network. In this study, we present a facile method to fabricate a biodegradable drug release platform that enables a magneto-thermally triggered drug release. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and thermo-responsive polymers within gelatin-based colloidal microgels, in conjunction with an alternating magnetic field application system.

We present a facile method to fabricate a biodegradable gelatin-based drug release platform that is magneto-thermally responsive. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and poly(N-isopropylacrylamide-co-acrylamide) within a spherical gelatin micro-network crosslinked by genipin, in conjunction with an alternating magnetic field application system.

制御された薬物放出のための磁場応答性ハイブリッドゼラチンマイクロゲルを交互に

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of ...

Rapid Scan Electron Paramagnetic Resonance Opens New Avenues for Imaging Physiologically Important Parameters In Vivo

We demonstrate a superior method of 2D spectral-spatial imaging of stable radical reporter molecules at 250 MHz using rapid-scan electron-paramagnetic-resonance (RS-EPR), which can provide quantitative information under in vivo conditions on oxygen concentration, pH, redox status and concentration of signaling molecules (i.e., OH&#8226;, NO&#8226;). The RS-EPR technique has a higher sensitivity, improved spatial resolution (1 mm), and shorter acquisition time in comparison to the standard continuous wave (CW) technique. A variety of phantom configurations have been tested, with spatial resolution varying from 1 to 6 mm, and spectral width of the reporter molecules ranging from 16 &#181;T (160 mG) to 5 mT (50 G). A cross-loop bimodal resonator decouples excitation and detection, reducing the noise, while the rapid scan effect allows more power to be input to the spin system before saturation, increasing the EPR signal. This leads to a substantially higher signal-to-noise ratio than in conventional CW EPR experiments.

Rapid Scan Electron Paramagnetic Resonance Opens New Avenues for Imaging Physiologically Important Parameters In Vivo

A new electron paramagnetic resonance (EPR) method, rapid scan EPR (RS-EPR), is demonstrated for 2D spectral spatial imaging which is superior to the traditional continuous wave (CW) technique and opens new venues for in vivo imaging. Results are demonstrated at 250 MHz, but the technique is applicable at any frequency.

高速走査電子常磁性共鳴イメージング生理学的に重要なパラメータのための新しい道を開きます。<em&gt;インビボ</em

We demonstrate a superior method of 2D spectral-spatial imaging of stable radical reporter molecules at 250 MHz using rapid-scan ...

Magnetic Levitation Coupled with Portable Imaging and Analysis for Disease Diagnostics

Currently, many clinical diagnostic procedures are complex, costly, inefficient, and inaccessible to a large population in the world. The requirements for specialized equipment and trained personnel require that many diagnostic tests be performed at remote, centralized clinical laboratories. Magnetic levitation is a simple yet powerful technique and can be applied to levitate cells, which are suspended in a paramagnetic solution and placed in a magnetic field, at a position determined by equilibrium between a magnetic force and a buoyancy force. Here, we present a versatile platform technology designed for point-of-care diagnostics which uses magnetic levitation coupled to microscopic imaging and automated analysis to determine the density distribution of a patient's cells as a useful diagnostic indicator. We present two platforms operating on this principle: (i) a smartphone-compatible version of the technology, where the built-in smartphone camera is used to image cells in the magnetic field and a smartphone application processes the images and to measures the density distribution of the cells and (ii) a self-contained version where a camera board is used to capture images and an embedded processing unit with attached thin-film-transistor (TFT) screen measures and displays the results. Demonstrated applications include: (i) measuring the altered distribution of a cell population with a disease phenotype compared to a healthy phenotype, which is applied to sickle cell disease diagnosis, and (ii) separation of different cell types based on their characteristic densities, which is applied to separate white blood cells from red blood cells for white blood cell cytometry. These applications, as well as future extensions of the essential density-based measurements enabled by this portable, user-friendly platform technology, will significantly enhance disease diagnostic capabilities at the point of care.

We present a magnetic levitation technique coupled with automated imaging and analysis in both a smartphone-compatible device and a device with embedded imaging and processing. This is applied to measure the density distribution of cells with two demonstrated biomedical applications: sickle cell disease diagnosis and separating white and red blood cells.

病の診断のためのポータブルイメージングおよび分析と相まって磁気浮上

Currently, many clinical diagnostic procedures are complex, costly, inefficient, and inaccessible to a large population in the world. The requirements for ...

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant &#34;burst release&#34; of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.

Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release

This manuscript describes the preparation of magnetic and thermal-sensitive microgels via a temperature-induced emulsion without chemical reaction. These sensitive microgels were synthesized by mixing poly(N-isopropylacrylamide) (PNIPAAm), polyethylenimine (PEI) and Fe3O4-NH2 nanoparticles for the potential use in magnetically and thermally triggered drug-release.

磁気および感熱性ポリ（<em&gt; N</em&gt; - イソプロピルアクリルアミド）ベースのミクロゲル

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...

Metabolic Support of Excised, Living Brain Tissues During Magnetic Resonance Microscopy Acquisition

This protocol describes the procedures necessary to support normal metabolic functions of acute brain slice preparations during the collection of magnetic resonance (MR) microscopy data. While it is possible to perform MR collections on living, excised mammalian tissue, such experiments have traditionally been constrained by resolution limits and are thus incapable of visualizing tissue microstructure. Conversely, MR protocols that did achieve microscopic image resolution required the use of fixed samples to accommodate the need for static, unchanging conditions over lengthy scan times. The current protocol describes the first available MR technique that enables imaging of living, mammalian tissue samples at microscopic resolutions. Such data is of great importance to the understanding of how pathology-based contrast changes occurring at the microscopic level influence the content of macroscopic MR scans such as those used in the clinic. Once such an understanding is realized, diagnostic methods with greater sensitivity and accuracy can be developed, which will translate directly to earlier disease treatment, more accurate therapy monitoring and improved patient outcomes.
While the described methodology focuses on brain slice preparations, the protocol is adaptable to any excised tissue slice given that changes are made to the gas and perfusate preparations to accommodate the tissue&#39;s specific metabolic needs. Successful execution of the protocol should result in living, acute slice preparations that exhibit MR diffusion signal stability for periods up to 15.5 h. The primary advantages of the current system over other MR compatible perfusion apparatuses are its compatibility with the MR microscopy hardware required to attain higher resolution images and ability to provide constant, uninterrupted flow with carefully regulated perfusate conditions. Reduced sample throughput is a consideration with this design as only one tissue slice may be imaged at a time.

The current protocol describes a method by which users can maintain viability of acute hippocampal and cortical slice preparations during the collection of magnetic resonance microscopy data.

代謝サポートの切除、生体脳磁気共鳴顕微鏡集録時に

This protocol describes the procedures necessary to support normal metabolic functions of acute brain slice preparations during the collection of magnetic ...

Measuring the Spin-Lattice Relaxation Magnetic Field Dependence of Hyperpolarized [1-13C]pyruvate

The fundamental limit to in vivo imaging applications of hyperpolarized 13C-enriched compounds is their finite spin-lattice relaxation times. Various factors affect the relaxation rates, such as buffer composition, solution pH, temperature, and magnetic field. In this last regard, the spin-lattice relaxation time can be measured at clinical field strengths, but at lower fields, where these compounds are dispensed from the polarizer and transported to the MRI, the relaxation is even faster and difficult to measure. To have a better understanding of the amount of magnetization lost during transport, we used fast field-cycling relaxometry, with magnetic resonance detection of 13C nuclei at ~0.75 T, to measure the nuclear magnetic resonance dispersion of the spin-lattice relaxation time of hyperpolarized [1-13C]pyruvate. Dissolution dynamic nuclear polarization was used to produce hyperpolarized samples of pyruvate at a concentration of 80 mmol/L and physiological pH (~7.8). These solutions were rapidly transferred to a fast field-cycling relaxometer so that relaxation of the sample magnetization could be measured as a function of time using a calibrated small flip angle (3&#176;-5&#176;). To map the T1 dispersion of the C-1 of pyruvate, we recorded data for different relaxation fields ranging between 0.237 mT and 0.705 T. With this information, we determined an empirical equation to estimate the spin-lattice relaxation of the hyperpolarized substrate within the mentioned range of magnetic fields. These results can be used to predict the amount of magnetization lost during transport and to improve experimental designs to minimize signal loss.

Measuring the Spin-Lattice Relaxation Magnetic Field Dependence of Hyperpolarized [1-13C]pyruvate

We present a protocol to measure the magnetic field dependence of the spin-lattice relaxation time of 13C-enriched compounds, hyperpolarized by means of dynamic nuclear polarization, using fast field-cycled relaxometry. Specifically, we have demonstrated this with [1-13C]pyruvate, but the protocol could be extended to other hyperpolarized substrates.

過偏光のスピン格子緩和磁場依存性の測定[1-13C]ピルビン酸

The fundamental limit to in vivo imaging applications of hyperpolarized 13C-enriched compounds is their finite spin-lattice relaxation times. Various ...

High-resolution Imaging of Nuclear Dynamics in Live Cells under Uniaxial Tensile Strain

Extracellular mechanical strain is known to elicit cell phenotypic responses and has physiological relevance in several tissue systems. To capture the effect of applied extracellular tensile strain on cell populations in vitro via biochemical assays, a device has previously been designed which can be fabricated simply and is small enough to fit inside tissue culture incubators, as well as on top of microscope stages. However, the previous design of the polydimethylsiloxane substratum did not allow high-resolution subcellular imaging via oil-immersion objectives. This work describes a redesigned geometry of the polydimethylsiloxane substratum and a customized imaging setup that together can facilitate high-resolution subcellular imaging of live cells while under applied strain. This substratum can be used with the same, earlier designed device and, hence, has the same advantages as listed above, in addition to allowing high-resolution optical imaging. The design of the polydimethylsiloxane substratum can be improved by incorporating a grid which will facilitate tracking the same cell before and after the application of strain. Representative results demonstrate high-resolution time-lapse imaging of fluorescently labeled nuclei within strained cells captured using the method described here. These nuclear dynamics data give insights into the mechanism by which applied tensile strain promotes differentiation of oligodendrocyte progenitor cells.&#160;

Using a previously designed device to apply mechanical strain to adherent cells, this paper describes a redesigned substratum geometry and a customized apparatus for high-resolution single-cell imaging of strained cells with a 100x oil immersion objective.

一軸引張ひずみ下での生細胞における核動態の高分解能イメージング

Extracellular mechanical strain is known to elicit cell phenotypic responses and has physiological relevance in several tissue systems. To capture the ...