Name: using extraordinary optical transmission to quantify cardiac biomarkers in human serum
Uploaded: 2017-12-13T12:30:00
Description: Watch this Scientific Journal Video about Using Extraordinary Optical Transmission to Quantify Cardiac Biomarkers in Human Serum at JoVE.com

美联社感谢文卡特山教授、新加坡国立大学纳米和纳米技术倡议和副校长办公室 (R-398-000-084-646) 的支持。CLD 承认新加坡卫生部国家医学研究理事会在其临床科学家资助计划 NMRC/CSA/035/2012 和新加坡国立大学的支持。资助者在研究设计、数据收集和分析、决定出版或准备原稿方面没有作用。

1. 传感器的制造和数据的获取
<ol>
	<li>镍模的制备
	<ol>
		<li>将一层220纳米厚的负电子束阻挡在600µm 厚的4的硅片上。使用电子束光刻系统编写该晶片上设计的纳米阵列。<ol>
			<li>为了加速电子束写入, 请为每个300µm 字段大小 (a) (即,在每个300µm2区域上映射4亿点, 并将每个点都由电子束或不显示, 以低 dotmap (N) 为20k 写入模式。, 具体取决于图案设计)。设置抗电子束抗照射...

<ol>
	<li>Ebbesen, T. W., Lezec, H. J., Ghaemi, H., Thio, T., Wolff, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extraordinary+optical+transmission+through+sub-wavelength+hole+arrays.">Extraordinary optical transmission through sub-wavelength hole arrays.</a> Nature. 391 (6668), 667-669 (1998).</li><li>Krishnan, 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=Evanescently+coupled+resonance+in+surface+plasmon+enhanced+transmission.">Evanescently coupled resonance in surface plasmon enhanced transmission.</a> Optics Comm. 200 (1), 1-7 (2001).</li><li>Yang, J. -. C., 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=Enhanced+optical+transmission+mediated+by+localized+plasmons+in+anisotropic,+three-dimensional+nanohole+arrays.">Enhanced optical transmission mediated by localized plasmons in anisotropic, three-dimensional nanohole arrays.</a> Nano letters. 10 (8), 3173-3178 (2010).</li><li>Kim, J. H., Moyer, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transmission+characteristics+of+metallic+equilateral+triangular+nanohole+arrays.">Transmission characteristics of metallic equilateral triangular nanohole arrays.</a> Appl Phys Lett. 89 (12), 121106 (2006).</li><li>Liu, H., Lalanne, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microscopic+theory+of+the+extraordinary+optical+transmission.">Microscopic theory of the extraordinary optical transmission.</a> Nature. 452 (7188), 728-731 (2008).</li><li>Shon, Y. -. S., Choi, H. Y., Guerrero, M. S., Kwon, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+of+nanostructured+film+arrays+for+transmission+localized+surface+plasmon+sensing.">Preparation of nanostructured film arrays for transmission localized surface plasmon sensing.</a> Plasmonics. 4 (2), 95-105 (2009).</li><li>Xiang, G., Zhang, N., Zhou, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Localized+surface+plasmon+resonance+biosensing+with+large+area+of+gold+nanoholes+fabricated+by+nanosphere+lithography.">Localized surface plasmon resonance biosensing with large area of gold nanoholes fabricated by nanosphere lithography.</a> Nanoscale Res Lett. 5 (5), 818 (2010).</li><li>Valsecchi, C., Brolo, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Periodic+metallic+nanostructures+as+plasmonic+chemical+sensors.">Periodic metallic nanostructures as plasmonic chemical sensors.</a> Langmuir. 29 (19), 5638-5649 (2013).</li><li>Gates, B. D., 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=New+approaches+to+nanofabrication:+molding,+printing,+and+other+techniques.">New approaches to nanofabrication: molding, printing, and other techniques.</a> Chem Rev. 105 (4), 1171-1196 (2005).</li><li>Guo, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanoimprint+lithography:+methods+and+material+requirements.">Nanoimprint lithography: methods and material requirements.</a> Adv Mater. 19 (4), 495-513 (2007).</li><li>Wong, T. I., 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=High+throughput+and+high+yield+nanofabrication+of+precisely+designed+gold+nanohole+arrays+for+fluorescence+enhanced+detection+of+biomarkers.">High throughput and high yield nanofabrication of precisely designed gold nanohole arrays for fluorescence enhanced detection of biomarkers.</a> Lab on a Chip. 13 (12), 2405-2413 (2013).</li><li>Deng, J., Wong, T. I., Sun, L. L., Quan, C., Zhou, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acceleration+of+e-beam+lithography+by+minimized+resist+exposure+for+large+scale+nanofabrication.">Acceleration of e-beam lithography by minimized resist exposure for large scale nanofabrication.</a> Microelect Eng. 166, 31-38 (2016).</li><li>Wu, L., Bai, P., Li, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Designing+surface+plasmon+resonance+of+subwavelength+hole+arrays+by+studying+absorption.">Designing surface plasmon resonance of subwavelength hole arrays by studying absorption.</a> JOSA B. 29 (4), 521-528 (2012).</li><li>Ding, T., 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=Quantification+of+a+cardiac+biomarker+in+human+serum+using+extraordinary+optical+transmission+(EOT).">Quantification of a cardiac biomarker in human serum using extraordinary optical transmission (EOT).</a> PloS one. 10 (3), 0120974 (2015).</li><li>Im, H., Sutherland, J. N., Maynard, J. A., Oh, S. -. 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通过模拟入射光和纳米结构之间的相互作用, 可以识别出合适的峰值 (在透射谱中), 其位移可记录为分析物浓度的函数。重要的是要注意, 对传感器结构的波段的本地化是至关重要的选择正确的波段, 其转移可以跟踪, 以感知分析物。可视化可以通过仿真实现。这也是关键的设计一个优化结构, 使传感的分析。正如这里所看到的, 第一和第三波段是在玻璃金色的界面上定位的, 因此对传感是无用的。在...

基于纳米阵列的化学传感器一直是许多调查的主题, 因为在 1998年1中, Ebbesen et al.发布了第一份关于特殊光传输 (EOT) 的报告。当光撞击波长维纳米结构的周期阵列时, 增强的透射在特定波长上发生。当入射光与极化 (BW) 和/或局部表面等离子体 (LSP)2时发生。
当与这样的周期数组传感时, 所利用的底层物理原理很简单。分子在金属界面上的吸附, 改变了介质在接触金属时的介电常数, 反过来又转移了光谱中传输波段的位置。频谱本身可以通过纳米工程来调整形状、大小和分离距离3,4,5。根据设计, 基于 EOT 的传感器在其光谱中具有特征波段, 在分子结合事件的调查过程中, 它能促进特定的赋值6、7、8 。这是一个关键的优势比商业可用表面等离子共振 (SPR) 平台。
使用 EOT 的传感器通常涉及光源的光学对准, 使准直光束在传感表面发生入射。生成大型纳米表面的技术 (如共聚模板和干涉和纳米光刻) 的重现性较差,9。由于这些限制在精确地制造出显示 EOT 现象的大表面, 需要光学显微镜来正确定位光源和探测器。为了简化技术, 采用了高质量的 nanoimprinting 光刻 (零)10 。这使得大的传感器表面区域的生产11 (毫米级), 消除了需要显微镜来寻找传感表面上的芯片。相反, 这种传感器可以很容易地与标准的光缆连接。
由于此纳米阵列的传输峰值包含在可见光近红外区域 (近红外线), 因此它非常适合于在水环境中感知生物分子的结合事件。模拟了纳米阵的期望光学行为。通过对标准折射率 (RI) 液体的研究, 验证了实验结果的正确性。该阵列用于测定心肌肌钙蛋白 i (cTnI) 在人血清复杂背景下的浓度。cTnI 是诊断急性心肌梗死的临床金标准。
使用该传感器, 可以检测和量化的 cTnI 在人血清中的检测限度 (LOD) 的 0.55 ng/毫升, 这是临床相关的。该检测比最常用的技术在这个领域, 酶联免疫吸附试验 (ELISA) 快得多。此外, 传感表面可以很容易地再生, 因此可重复使用。因此, 这项工作表明, 纳米阵列的承诺, 作为一个可行的点 (POC) 技术的传感在复杂的 biofluids。

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			<td height="43" style="height:43px;width:199px;">Electron Beam Lithography setup</td>
			<td style="width:220px;">Elionix ELS 700</td>
			<td style="width:199px;"></td>
			<td style="width:91px;"></td>
		</tr>
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			<td height="22" style="height:22px;width:199px;">o-Xylene</td>
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			<td style="width:199px;">95662</td>
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		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:199px;">EB resist</td>
			<td style="width:220px;">Sumitomo</td>
			<td style="width:199px;">NEB-22A2</td>
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		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:199px;">Developer reagent</td>
			<td style="width:220px;">Shipley Company</td>
			<td style="width:199px;">Microposit MF 321</td>
			<td style="width:91px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:199px;">Electroplating machine</td>
			<td style="width:220px;">Technotrans AG RD 50</td>
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			<td height="43" style="height:43px;width:199px;">Photoresist stripper&#160;</td>
			<td style="width:220px;">Rohm and Haas Electronic Materials&#160;LLC</td>
			<td style="width:199px;">Microposit Remover 1165</td>
			<td style="width:91px;"></td>
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		<tr height="22">
			<td height="22" style="height:22px;width:199px;">Etching System</td>
			<td style="width:220px;">Trion Phantom</td>
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			<td height="43" style="height:43px;width:199px;">Heptadecafluoro-1,1,2,2-tetrahydrodecyl)trichlorosilane&#160;</td>
			<td style="width:220px;">Gelest (PA, USA)</td>
			<td style="width:199px;">78560-44-8</td>
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			<td height="22" style="height:22px;width:199px;">SAM coater&#160;</td>
			<td style="width:220px;">Sorona Inc.</td>
			<td style="width:199px;">AVC 150M</td>
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			<td height="22" style="height:22px;width:199px;">Photo-curable NIL resist</td>
			<td style="width:220px;">micro resist technology GmbH</td>
			<td style="width:199px;">mr-UVCur21-300nm</td>
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			<td height="22" style="height:22px;width:199px;">Light Curing System</td>
			<td style="width:220px;">Dymax&#160;</td>
			<td style="width:199px;">Model 2000 Flood</td>
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			<td height="22" style="height:22px;width:199px;">E-beam deposition machine</td>
			<td style="width:220px;">Denton Explorer</td>
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			<td height="43" style="height:43px;width:199px;">UV-visible spectrometer&#160;</td>
			<td style="width:220px;">Ocean optic HR2000+ (Dunedin, FL, USA)</td>
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			<td height="43" style="height:43px;width:199px;">Standard refractive index liquids&#160;</td>
			<td style="width:220px;">Cargill Inc (Cedar Grove, USA)</td>
			<td style="width:199px;">18032</td>
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			<td height="22" style="height:22px;width:199px;">Plotting software</td>
			<td style="width:220px;">Origin</td>
			<td style="width:199px;">Origin Pro 9</td>
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		<tr height="22">
			<td height="22" style="height:22px;width:199px;">10-carboxy-1-decanethiol&#160;</td>
			<td style="width:220px;">Dojindo Laboratories (Japan)</td>
			<td style="width:199px;">C385-10</td>
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			<td height="22" style="height:22px;width:199px;">1-octanethiol&#160;</td>
			<td style="width:220px;">Sigma-Aldrich, MO, USA</td>
			<td style="width:199px;">471386</td>
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			<td height="85" style="height:85px;width:199px;">Sulfo-N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide&#160;</td>
			<td style="width:220px;">BioRad (CA, USA)</td>
			<td style="width:199px;">1762410</td>
			<td style="width:91px;"></td>
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			<td height="22" style="height:22px;width:199px;">Anti-troponin antibody 560</td>
			<td style="width:220px;">Hytest (Finland)</td>
			<td style="width:199px;">4T21</td>
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			<td height="22" style="height:22px;width:199px;">Ethanolamine-HCl solution</td>
			<td style="width:220px;">BioRad (CA, USA)</td>
			<td style="width:199px;">1762450</td>
			<td style="width:91px;"></td>
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			<td height="43" style="height:43px;width:199px;">Surface Plasmon Resonance setup</td>
			<td style="width:220px;">BioRad XPR36 (Haifa, Israel)</td>
			<td style="width:199px;"></td>
			<td style="width:91px;"></td>
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			<td height="22" style="height:22px;width:199px;">Multiplexed SPR chip</td>
			<td style="width:220px;">BioRad</td>
			<td style="width:199px;">GLC</td>
			<td style="width:91px;"></td>
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		<tr height="22">
			<td height="22" style="height:22px;width:199px;">Human cTnI standard</td>
			<td style="width:220px;">Phoenix Pharmaceuticals</td>
			<td style="width:199px;">EK -311-05</td>
			<td style="width:91px;"></td>
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		<tr height="22">
			<td height="22" style="height:22px;width:199px;">Glycine-HCl</td>
			<td style="width:220px;">BioRad (CA, USA)</td>
			<td style="width:199px;">1762221</td>
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</table>

using extraordinary optical transmission to quantify cardiac biomarkers in human serum

对于一个传感平台具有临床相关性的点 (POC) 的设置, 化验灵敏度, 重现性, 并能够可靠地监测分析的背景下, 人血清是至关重要的。
Nanoimprinting 光刻 (零) 被用来制造, 在低成本, 传感面积高达1.5 毫米 x 1.5 毫米。传感面是由高保真阵列的 nanoholes, 每一个面积约 140 nm2。零的巨大再现性使得在12个单独制造的表面上使用一个单芯片的单测量策略成为可能, 最小的芯片变化。这些 nanoimprinted 的局部表面等离子体共振 (LSPR) 芯片被广泛测试的能力, 以可靠地测量 bioanalyte 在浓度变化, 从2.5 到 75 ng/毫升在一个复杂的背景 biofluid-in 这种情况下, 人血清。零的高保真度使产生大的传感区, 这反过来又消除了对显微镜的需要, 因为这种生物传感器可以很容易地与一个普通的实验室光源接口。这些生物传感器可以检测高灵敏度的血清心肌肌钙蛋白, 在 0.55 ng/毫升的检测限度 (LOD), 这是临床相关的。它们也显示出低的芯片方差 (由于制造过程的高质量)。结果是相称与广泛使用的酶联免疫吸附试验 (ELISA) 的基础上, 但该技术保留了 LSPR-based 传感平台的优势 (即,可的小型化和多路复用, 使其更适合于 POC 应用程序)。

用于测量的光学设置显示在图 1A中。在图 1B中给出了实际纳米数组的图像。为了了解物理驱动传感过程, 利用 COMSOL 仿真软件模拟了浆场在水环境中的分布。模拟结果与实测值有关。先前发布的研究包含了所做假设的详细信息和模拟1113中使用的参数。用于模拟纳米阵列的浆场的物理尺...

Watch this Scientific Journal Video about Using Extraordinary Optical Transmission to Quantify Cardiac Biomarkers in Human Serum at JoVE.com

Using Extraordinary Optical Transmission to Quantify Cardiac Biomarkers in Human Serum

这项工作描述了 nanoimprinting 光刻方法, 制造高质量的传感阵列的工作原理, 非凡的光传输。该生物传感器成本低廉, 健壮, 易于使用, 并能检测血清心肌肌钙蛋白 i 在临床相关浓度 (99th百分比截止∼10-400 pg/毫升, 取决于化验)。

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A detailed  understanding of the complexity and relative variability within the human  cardiac venous system is crucial for the development of cardiac ...

Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy

定义人工程心脏组织建设探讨心肌细胞疗法的机理

Human cardiac tissue engineering can fundamentally impact therapeutic discovery through the development of new species-specific screening systems that ...

Transmission of Multiple Signals through an Optical Fiber Using Wavefront Shaping

通过光纤使用波前整形多个信号的传输

The transmission of multiple independent optical signals through a multimode fiber is accomplished using wavefront shaping in order to compensate for the ...

Optical Imaging of Isolated Murine Ventricular Myocytes

分离的月毛心室肌细胞的光学成像

The ability to isolate adult cardiac myocytes has permitted researchers to study a variety of cardiac pathologies at the single cell level. While advances ...

Cerebral Blood Flow-Based Resting State Functional Connectivity of the Human Brain using Optical Diffuse Correlation Spectroscopy

使用光学漫反射相关光谱，基于脑血流的休息状态功能连接

To obtain a comprehensive understanding of the human brain, utilization of cerebral blood flow (CBF) as a source of contrast is desired because it is a ...

Preclinical Cardiac Electrophysiology Assessment by Dual Voltage and Calcium Optical Mapping of Human Organotypic Cardiac Slices

人体器官性心脏切片双电压和钙光学映射的临床前心脏电生理评估

Human cardiac slice preparations have recently been developed as a platform for human physiology studies and therapy testing to bridge the gap between ...

Fabrication of 3D Cardiac Microtissue Arrays using Human iPSC-Derived Cardiomyocytes, Cardiac Fibroblasts, and Endothelial Cells

使用人iPSC衍生的心肌细胞，心脏成纤维细胞和内皮细胞制造3D心脏微组织阵列

Generation of human cardiomyocytes (CMs), cardiac fibroblasts (CFs), and endothelial cells (ECs) from induced pluripotent stem cells (iPSCs) has provided ...