Name: insertion of flexible neural probes using rigid stiffeners attached with biodissolvable adhesive
Uploaded: 2013-09-27T13:00:00
Description: Watch this Scientific Journal Video about Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive at JoVE.com

这项工作是由美国国立卫生研究院NIDCD Y1-DC-8002-01的支持。根据合同DE-AC52-07NA27344美国能源署的主持下进行了劳伦斯利弗莫尔国家实验室这项工作。

1。探头大会补强本节中的协议的描述制造的硅加劲肋，并且薄膜的聚合物探针的装配到刚性元件， 图1示出了沿与提出的加强件的典型聚合物的神经探针。的加强筋设计的细节示于图2。这种设计的新颖特征是在浅“芯吸”通道沿其长度是用来在组装过程中分配液体粘合剂运行。加强板的较宽部分为装配和外科插入时处理的标签。该选项卡上的水库连?...

<ol>
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这里描述的方法提供了一个良好的控制过程附加薄膜聚合物探针来分离加强筋与biodissolvable粘合剂。还提出，建议外科手术，以实现这些可移动的加强筋和技术验证过程在体外对于一个给定探针加强筋的配置。由于加强件可以由任意刚性的，该方法可以方便地插入相对长的探针（&gt; 3mm）的中。因此，该插入方法有望成为一个有利的技术在脑深部刺激（DBS），脊髓刺激，和外周神经接口的应...

微电极阵列在神经科学的一个重要工具，以及新兴的临床应用，如假肢。特别是，插入的微电极探针通过与细胞在大脑，脊髓和周围神经亲密接触使刺激神经元的活动和记录。对于植入式神经探针的一个主要挑战是稳定的刺激和记录功能，延年益寿。微电极探针和神经组织之间的相互作用的建模和实验研究表明，1机制降解是微撕裂神经组织，由于在探头和组织1-3之间轻微的相对运动。一种解决方案是制造匹配更紧密神经组织，以减少相对微动的体积压缩刚度特性灵活的探针。因此，生物相容的薄膜的聚合物，例如聚酰亚胺和聚对二甲苯已被采用为有利的基板为微电子处接上的电流探头4-8。 柔性探头的权衡是，他们是难以插入到神经组织。研究人员已经采取了各种方法，以便于插入的柔性探头，同时保留所希望的机械性能。一类设计的修改聚合物探针的几何形状，同时遵守其他地区，以增加刚度在某些部分或轴。这已经完成通过将肋或其它材料9,10层。另一种方法中集成了一个3-D信道到聚合物探针设计填充有可生物降解的材料11。该探针可以被临时硬化，并插入该材料在通道中溶解并排出，之后。然而，方法如上述那永久修改最终植入的装置的几何形状可能会损害一些的柔性探针的理想特征。 一种方法，做Ñ加时改变最终探针的几何形状是封装在聚合物装置与可生物降解的材料，以暂时硬化装置12-14。然而，典型的可生物降解材料具有的杨氏模量幅度比硅小的订单，并作相应需要更大的厚度，以达到相同的刚度。充分涂覆探针可产生更圆的或钝头，使得插入更加困难。此外，由于可分解涂层暴露，有他们的危险接触后立即溶解，甚至近在咫尺，与组织。 另一类方法采用新型探头的基板材料，以减少刚度被植入组织后。这样的材料包括形状记忆聚合物15和一个机械适应性纳米复合材料16。这些材料能够在弹性模量显著插入后下降，并可能导致探针更紧密MATC神经组织h的机械性能。然而，刚性的可实现的范围仍然是有限的，因此它们可能不能够提供非常高的刚度等于硅或钨丝。因此，在柔性探针是很长的（ 例如 &gt; 3毫米），或具有非常低的刚度的情况下，可能仍然需要的临时固定更刚性的加强筋的方法。 报道又一个有前途的方法是涂层具有永久自组装单层（SAM）来定制班车和灵活的探头17之间的表面相互作用的加强班车。在干燥时，探针附着于涂穿梭静电。插入后，水将迁移到该亲水表面，从航天飞机分离探针，使得往复可以被提取。穿梭萃取减小探针位移被证明（85微米）。然而，仅静电相互作用保持探头吨他穿梭，有探头打滑相对于航天飞机之前和期间插入一定的风险。 我们已经开发了在该柔性探头连接到与该牢固地保持在插入过程中探针的临时biodissolvable粘合剂材料的加强件的方法。所用的探针是聚酰亚胺，其具有2-4京帕数量级的弹性模量进行。加强件是由硅制成，具有〜为200GPa的弹性模量。在连接时，硅的刚性支配，便于插入。一旦插入到组织中，粘合剂材料溶解和加强件被提取到探针恢复到其初始的灵活性。我们选择了聚乙二醇（PEG）作为biodissolvable粘合材料。 PEG已被用于在植入的应用，如神经探针，组织工程和药物递送11,18,19。一些证据表明，PEG可以减轻神经炎症反应在脑组织18,20。相对于其他可能的材料，包括蔗糖，聚乳酸 - 共 - 乙醇酸（PLGA），和聚乙烯醇（PVA），聚乙二醇具有的溶解时间在生物流体，它是一个合适的规模对许多植入手术（数量级几十分钟，这取决于分子量）。此外，它是固体在室温和液体温度范围为50-65℃。这个属性使得它特别适合于我们的精密装配过程。此外，在17个类似的SAM所描述的，溶解PEG是亲水性的，有利于提取的加强筋。这种有利的做法是由一种新型的加强筋设计和有条不紊的装配工艺，确保均匀的粘合剂覆盖面和准确的和可重复的对齐方式启用。除了 ​​装配过程中，我们提出了在手术过程中实现可移动的加强件的方法，以及在体外程序来评价提取STI的ffener。 这里介绍的协议假定用户具有柔性聚合物微电极探针。关于这个探头的加强筋与组件的制造到加强筋的协议的一部分，假设获得的微细加工设备中常见的工具。有关插入和提取的协议可能会在神经科学为导向的实验室进行。

<table border="1">
		<tbody>
		 <tr>
			<td>Name of Reagent/Material</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		 </tr>
		 <tr>
			<td>Polyethylene glycol, 10,000 g/mol</td>
			<td>Sigma Aldrich</td>
			<td>309028</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Agarose</td>
			<td>Sigma Aldrich</td>
			<td>A9539</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Flexible Sub-micron Die Bonder</td>
			<td>Finetech</td>
			<td>Fineplacer lambda</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Micromanipulator</td>
			<td>KOPF</td>
			<td>1760-61</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Digital Microscope</td>
			<td>Hirox</td>
			<td>KH-7700</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Dual Illumination Revolver Zoom Lens</td>
			<td>Hirox</td>
			<td>MXG-2500REZ</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Precision Motorized Actuator</td>
			<td>Newport</td>
			<td>LTA-HS</td>
			<td>w/ CONEX-CC controller</td>
		 </tr>
		</tbody>
 </table>

insertion of flexible neural probes using rigid stiffeners attached with biodissolvable adhesive

预期微电极阵列所做生物相容性薄膜聚合物的神经接口设备已经扩展功能寿命，因为柔性材料可以减少因微动不良组织反应。然而，他们的灵活性，防止它们被准确地插入到神经组织。本文介绍的方法，以一种灵活的微电极探针临时性地连接到刚性加强板使用biodissolvable聚乙二醇（PEG），以促进所述探针的精确，手术插入。一个独特的加强筋的设计允许对PEG粘合剂的均匀分布沿着探针的长度。倒装芯片接合，在微电子封装中使用的常用工具，能够进行精确的和可重复的对准和连接的探针与加强筋。探针和加强件被手术植入在一起，然后将PEG使其溶解，使得加强筋可以被提取离开探头到位。最后， 在体外试验方法用于评价加强筋提取脑组织的琼脂糖凝胶模型。这种方法植入已被证明更长的柔性探头特别有利的（&gt; 3毫米）。它还提供了植入双面柔性探头一个可行的方法。迄今为止，该技术已被用来获得从大鼠皮层各种体内的记录数据。

这种插入技术被用于与LLNL的薄膜聚酰亚胺探头，它已通过ISO 10993生物相容性标准，并适用于慢性植入相结合。一个典型的薄膜聚酰亚胺探针沿着与硅刚性元件是大约10毫米长的狭窄区域， 如图1所示。此加强筋具有沿其长度延伸的1毛细通道， 如图2，图3示出了用于创建该加强筋出硅的mimcrofabrication过程， 图4示出固体的PEG的沉淀，它被放置成片的油藏，通过倒...

Watch this Scientific Journal Video about Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive at JoVE.com

Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive

的柔性神经微探针插入是通过将探针以刚性加强板与聚乙二醇（PEG）使能。独特的装配工艺确保了统一的和可重复的附件。插入到组织中后，所述PEG溶解和加强件被提取。 体外试验方法评估在琼脂糖凝胶的技术。

柔性神经微探针的使用附加与Biodissolvable胶粘剂刚性加劲肋插入

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Growing number of studies show that biomechanical properties of individual cells play major roles in multiple cellular functions, including cell ...

Creating Adhesive and Soluble Gradients for Imaging Cell Migration with Fluorescence Microscopy

创建的胶粘剂和可溶性梯度荧光显微镜成像细胞迁移

Cells can sense and migrate towards higher concentrations of adhesive cues such as the glycoproteins of the extracellular matrix and soluble cues such as ...

Fabrication and Implantation of Miniature Dual-element Strain Gages for Measuring In Vivo Gastrointestinal Contractions in Rodents.

Fabrication and Implantation of Miniature Dual-element Strain Gages for Measuring In Vivo Gastrointestinal Contractions in Rodents.

的微型双元应变计测量加工和植入<em&gt;体内</em&gt;胃肠收缩鼠害。

Gastrointestinal dysfunction remains a major cause of morbidity and mortality. Indeed, gastrointestinal (GI) motility in health and disease remains an ...

Using Adhesive Patterning to Construct 3D Paper Microfluidic Devices

使用粘性图案构建3D纸微流体装置

We demonstrate the use of patterned aerosol adhesives to construct both planar and nonplanar 3D paper microfluidic devices. By spraying an aerosol ...

Force System with Vertical V-Bends: A 3D In Vitro Assessment of Elastic and Rigid Rectangular Archwires

Force System with Vertical V-Bends: A 3D In Vitro Assessment of Elastic and Rigid Rectangular Archwires

垂直 V 形弯曲力系统: 3D 弹性和刚性矩形矫正线的体外评价

A proper understanding of the force system created by various orthodontic appliances can make treatment of patients efficient and predictable. Reducing ...

Rat Model of Adhesive Capsulitis of the Shoulder

肩上粘 Capsulitis 大鼠模型的建立

This proposal aims to create an in vivo rat model of adhesive capsulitis for researching potential treatment options for this condition and other ...

Increasing Durability of Dissociated Neural Cell Cultures Using Biologically Active Coralline Matrix

使用生物活性珊瑚基质提高解离神经细胞培养物的耐久性

Cultures of dissociated hippocampal neuronal and glial cells are a valuable experimental model for studying neural growth and function by providing high ...

A Flexible Chamber for Time-Lapse Live-Cell Imaging with Stimulated Raman Scattering Microscopy

用于使用受激拉曼散射显微镜进行延时活细胞成像的柔性腔室

Stimulated Raman scattering (SRS) microscopy is a label-free chemical imaging technology. Live-cell imaging with SRS has been demonstrated for many ...