Name: fabrication of fine electrodes on the tip of hypodermic needle using photoresist spray coating and flexible photomask for biomedical applications
Uploaded: 2017-11-28T14:00:00
Description: Watch this Scientific Journal Video about Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications at JoVE.com

这项工作得到了 "生物医学综合技术研究" 项目的支持, 其依据是2017年提供的一项赠款。

1. 皮下针的电绝缘
注: 采用透明热收缩管 (哈勃), 用于720µm 直径和32毫米的皮下针的电绝缘。该望远镜是由聚对苯二甲酸乙二醇酯 (PET), 它显示了良好的化学抗性, 大多数酸和碱, 优良的机械耐久性, 和生物相容。该望远镜的初始内径和壁厚分别为840µm 和25µm。在100° c 的温度下, 哈勃望远镜的直径往往会减少50% 以上, 在更高的温度下更能降低到190° c。请注意, PET 哈勃望远镜是一?...

<ol>
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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=Electrical+Cell-Substrate+Impedance+Spectroscopy+Can+Monitor+Age-Grouped+Human+Adipose+Stem+Cell+Variability+During+Osteogenic+Differentiation.">Electrical Cell-Substrate Impedance Spectroscopy Can Monitor Age-Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation.</a> Stem Cells Transl Med. , (2016).</li><li>Messina, W., Fitzgerald, M., Moore, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=SEM+and+ECIS+Investigation+of+Cells+Cultured+on+Nanopillar+Modified+Interdigitated+Impedance+Electrodes+for+Analysis+of+Cell+Growth+and+Cytotoxicity+of+Potential+Anticancer+Drugs.">SEM and ECIS Investigation of Cells Cultured on Nanopillar Modified Interdigitated Impedance Electrodes for Analysis of Cell Growth and Cytotoxicity of Potential Anticancer Drugs.</a> Electroanalysis. 28 (9), 2188-2195 (2016).</li><li>Abdolahad, 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=Single-cell+resolution+diagnosis+of+cancer+cells+by+carbon+nanotube+electrical+spectroscopy.">Single-cell resolution diagnosis of cancer cells by carbon nanotube electrical spectroscopy.</a> Nanoscale. 5 (8), 3421-3427 (2013).</li><li>Lee, 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=An+endoscope+with+integrated+transparent+bioelectronics+and+theranostic+nanoparticles+for+colon+cancer+treatment.">An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment.</a> Nat Commun. 6, 10059 (2014).</li><li>Haemmerich, D., Schutt, D. 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H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrical+impedance+spectroscopy+on+a+needle+for+safer+Veress+needle+insertion+during+laparoscopic+surgery.">Electrical impedance spectroscopy on a needle for safer Veress needle insertion during laparoscopic surgery.</a> Sens Actuator B-Chem. 250, 453-460 (2017).</li><li>Yun, J., Kim, H. W., Lee, J. -. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improvement+of+Depth+Profiling+into+Biotissues+Using+Micro+Electrical+Impedance+Spectroscopy+on+a+Needle+with+Selective+Passivation.">Improvement of Depth Profiling into Biotissues Using Micro Electrical Impedance Spectroscopy on a Needle with Selective Passivation.</a> Sensors. 16 (12), 2207 (2016).</li><li>Yun, J., 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=Micro+electrical+impedance+spectroscopy+on+a+needle+for+ex+vivo+discrimination+between+human+normal+and+cancer+renal+tissues.">Micro electrical impedance spectroscopy on a needle for ex vivo discrimination between human normal and cancer renal tissues.</a> Biomicrofluidics. 10 (3), 034109 (2016).</li><li>Kim, H. W., Yun, J., Lee, J. Z., Shin, D. G., Lee, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+Electrical+Impedance+Spectroscopy-on-a-Needle+as+a+Novel+Tool+to+Determine+Optimal+Surgical+Margin+in+Partial+Nephrectomy.">Evaluation of Electrical Impedance Spectroscopy-on-a-Needle as a Novel Tool to Determine Optimal Surgical Margin in Partial Nephrectomy.</a> Adv Healthc. , (2017).</li><li>Wu, 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=Conformal+Pad-Printing+Electrically+Conductive+Composites+onto+Thermoplastic+Hemispheres:+Toward+Sustainable+Fabrication+of+3-Cents+Volumetric+Electrically+Small+Antennas.">Conformal Pad-Printing Electrically Conductive Composites onto Thermoplastic Hemispheres: Toward Sustainable Fabrication of 3-Cents Volumetric Electrically Small Antennas.</a> PLoS One. 10 (8), e0136939 (2015).</li><li>Ahn, 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=Direct+fabrication+of+thin+film+gold+resistance+temperature+detection+sensors+on+a+curved+surface+using+a+flexible+dry+film+photoresist+and+their+calibration+up+to+450&#176;+C.">Direct fabrication of thin film gold resistance temperature detection sensors on a curved surface using a flexible dry film photoresist and their calibration up to 450&#176; C.</a> C. J Micromech Microeng. 23 (6), 065031 (2013).</li><li>Goluch, E. 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=Microfluidic+method+for+in-situ+deposition+and+precision+patterning+of+thin-film+metals+on+curved+surfaces.">Microfluidic method for in-situ deposition and precision patterning of thin-film metals on curved surfaces.</a> Appl Phys Lett. 85 (16), 3629-3631 (2004).</li><li>Hu, X., 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=A+degradable+polycyclic+cross-linker+for+UV-curing+nanoimprint+lithography.">A degradable polycyclic cross-linker for UV-curing nanoimprint lithography.</a> J Mater Chem C. 2 (10), 1836-1843 (2014).</li><li>Wu, J. -. T., Lai, H. -. C., Yang, S. -. Y., Huang, T. -. C., Wu, S. -. 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我们证明, 使用喷涂涂层和胶片掩的光刻是一种可行的方法, 在一个小直径小于1毫米的皮下针的曲面上制造精细的 ide。ide 的宽度和间隙均低至20µm, 而尖端的加工余量则小至680µm。在协议中, 对齐过程 (包括楔形错误删除) 是一个关键步骤。该产品的产量超过 90%, 当该公司通过严格的对准过程单独制造。这表明, 所提出的制造方法有可能发展为散装生产以可承受的价格。
对 PBS, ?...

皮下针被广泛用于医院的活检和药物传递, 因为它们价格低廉, 易于使用。他们也有优良的机械性能, 尽管他们的薄直径和锋利的结构适合入侵。在活检中, 靶组织在皮下注射针头的中空取样, 超声引导1。虽然超声检查是没有辐射, 安全的胎儿和孕妇, 并提供 real-time 成像, 很难看到身体深处的器官, 特别是在肥胖患者的情况下, 因为超声波不能穿透空气或脂肪组织2。此外, 外科医生无法从 two-dimensional 超声中获取深度信息, 这是大多数医院常规使用的, 因此, 如果医生缺乏技能或经验, 需要进行多次活检。在给药的脊髓麻醉, 医生确定, 针已达到脊髓的空间, 如果脑脊液 (CSF) 回流到注射器, 而小心插入到病人的背部针。确认脑脊液回流后, 将麻醉药注入脊髓间隙3。然而, 医生的风险穿透或切断神经纤维在脊柱的空间, 造成严重的疼痛病人, 甚至截瘫4,5。因此, 这个过程也需要一个熟练的医生。克服和减轻上述困难的一个解决办法是在皮下注射针头上添加一个导航功能, 以便能够提供关于针头位置的客观信息。这将有助于医生随时进行活检, 药物传递, 甚至手术, 而不依赖于他们的经验判断只。
为了在人体内电定位靶组织, 采用电阻抗谱 (EIS) 传感器的皮下针作为 EIS-on-a 针 (永世)6。EIS 传感器目前用于生物医学工程领域的应用, 如 DNA 检测7,8,9, 细菌/病毒检测10,11,12, 并分析细胞/组织13,14,15,16,17,18,1920,21,22. 在频率域中, 基于电导率和介电常数, 可以区分不同的材料。对磷酸缓冲盐水 (PBS)23、猪脂肪/肌肉组织的6、23、甚至人类肾脏正常/癌症组织的不同浓度水平的鉴别能力进行了验证24 ,25。这一能力的永世预计将大大提高活检的准确性, 通过定位靶组织的基础上的不同, 在电子阻抗的目标病变组织和相邻的正常组织。以类似的方式, 调查药物注射空间 (脊椎或硬膜外间隙) 和周围组织之间的电阻阻抗的差异可以帮助医生在确切的靶位置提供麻醉药物。此外, 可以用来电刺激大脑/肌肉, 以及确定在手术中的最佳手术切口, 涉及部分切除肿瘤, 如部分肾切除, 以保持尽可能多的正常组织可能.
在实现的最大的挑战之一是在皮下针的弯曲表面上的电极制造有一个小半径的曲率。使用传统的光刻工艺的直接金属图案被认为不适合在直径为几毫米或更小的弯曲衬底上制造微米电极。到目前为止, 各种方法, 包括共形印刷26, 柔性干膜光刻胶的27, 微流控方法28, 压光刻29, 和基板旋转光刻30, 已介绍了在曲面上制造金属/聚合物的模式。然而, 由于所要求的, 如所需的基板直径小于1毫米, 总电极长度为20毫米或以上, 宽度和间隙的电极范围在几十微米, 和高批量生产, 仍然有限制。
在本研究中, 提出了采用光刻胶喷涂和柔性膜掩的直接金属模式来实现皮下针曲面上的微米电极。针的直径和720µm (22 口径) 一样小, 广泛用于医院的活检和药物传递。并对所提出的制造方法的产量进行评估, 以确定以可承受的价格批量生产的可行性。

<table>
	<tbody>
		<tr>
			<td>Heat shrink tube</td>
			<td>VENTION MEDICAL, Inc.</td>
			<td>103-0655</td>
			<td></td>
		</tr>
		<tr>
			<td>Hypodermic needle (22G)</td>
			<td>HWAJIN MEDICAL co. ltd</td>
			<td>-</td>
			<td>http://www.hwajinmedical.com</td>
		</tr>
		<tr>
			<td>Heat gun</td>
			<td>Weller</td>
			<td>WHA600</td>
			<td>http://www.weller-tools.com/en/Home.html</td>
		</tr>
		<tr>
			<td>Ultrasonic cleaner</td>
			<td>HWASHIN INSTRUMENT CO, LTD.</td>
			<td>POWERSONIC 620-</td>
			<td>http://www.hwashin.net</td>
		</tr>
		<tr>
			<td>Hotplate</td>
			<td>AS ONE Corporation</td>
			<td>006560</td>
			<td></td>
		</tr>
		<tr>
			<td>Sputtering</td>
			<td>A-Tech System. Ltd.</td>
			<td>ATS/SPT/0208F</td>
			<td>http://www.atechsystem.co.kr</td>
		</tr>
		<tr>
			<td>Glass slide</td>
			<td>Paul Marienfeld GmbH &#38; Co. KG</td>
			<td>1000412</td>
			<td></td>
		</tr>
		<tr>
			<td>Spray coater</td>
			<td>LITHOTEK</td>
			<td>LSC-200</td>
			<td></td>
		</tr>
		<tr>
			<td>Photoresist</td>
			<td>AZ electronic materials</td>
			<td>GXR 601</td>
			<td>http://www.merck-performance-materials.com/en/index.html</td>
		</tr>
		<tr>
			<td>Developer (solution)</td>
			<td>AZ electronic materials</td>
			<td>MIF 300</td>
			<td>http://www.merck-performance-materials.com/en/index.html</td>
		</tr>
		<tr>
			<td>Aligner</td>
			<td>MIDAS SYSTEM CO.,Ltd.</td>
			<td>MDA-400M</td>
			<td>http://www.midas-system.com</td>
		</tr>
		<tr>
			<td>Microscope</td>
			<td>NIKON Corporation</td>
			<td>L200</td>
			<td>http://www.nikonmetrology.com</td>
		</tr>
		<tr>
			<td>Au wet etchant</td>
			<td>TRANSENE COMPANY, Inc.</td>
			<td>Au etchant type TFA</td>
			<td>http://transene.com</td>
		</tr>
		<tr>
			<td>Cr wet etchant</td>
			<td>KMG Electronic. Chemicals, Inc.</td>
			<td>CR-7</td>
			<td>http://kmgchemicals.com</td>
		</tr>
		<tr>
			<td>Au target</td>
			<td>Thin films and Fine Materials</td>
			<td>-</td>
			<td>http://www.thifine.co.kr</td>
		</tr>
		<tr>
			<td>Cr target</td>
			<td>Thin films and Fine Materials</td>
			<td>-</td>
			<td>http://www.thifine.co.kr</td>
		</tr>
		<tr>
			<td>Argon gas (99.999%)</td>
			<td>SINIL Gas Co.Ltd</td>
			<td>-</td>
			<td>http://www.sigas.kr</td>
		</tr>
		<tr>
			<td>Acetone solution</td>
			<td>OCI Company Ltd</td>
			<td>-</td>
			<td>http://www.ocicorp.co.kr/company/index.asp</td>
		</tr>
		<tr>
			<td>Impedance analyzer</td>
			<td>Gamry Instruments Inc</td>
			<td>Reference 600</td>
			<td>https://www.gamry.com</td>
		</tr>
		<tr>
			<td>Height Controller</td>
			<td>Mitutoyo Corporation</td>
			<td>192-613</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphate buffered saline</td>
			<td>Life Technologies Corporation</td>
			<td>10010023</td>
			<td></td>
		</tr>
	</tbody>
</table>

fabrication of fine electrodes on the tip of hypodermic needle using photoresist spray coating and flexible photomask for biomedical applications

我们介绍了一种电子阻抗谱 (EIS)--针 (EIS-on-a 针) 的制作方法, 通过测量和分析不同组织之间电阻阻抗的差异来定位体内的靶组织。本文介绍了用光刻胶喷涂和柔性膜掩在光刻工艺中, 在皮下针尖端指电极 (ide) 的制作方法。采用25µm 壁厚的聚对苯二甲酸乙二醇酯 (PET) 热收缩管作为绝缘和钝化层。与聚 (p-xylylene) 聚合物相比, 它具有更高的机械耐久性, 被广泛用作介质涂层材料。此外, 哈勃望远镜对大多数酸和碱具有良好的耐化学性, 这有利于限制化学物质对永世的损害。对化学/生物材料或使用酸性/碱性化学制品的制造而言, 使用 "永世" 尤其可取。该 ide 的制造间隙和宽度均为20µm, 其总宽度和长度分别为400µm 和860µm。皮下针的制作余量 (皮下注射针头尖端与 ide 起始点之间的距离) 小至680µm, 这表明在组织中可以避免不必要的过度侵入电阻阻抗测量。该方法具有很高的临床应用潜力, 如甲状腺活检和脊髓间隙麻醉药物的传递。此外, 即使在涉及部分切除肿瘤的手术中, 也可以通过检测手术切口 (与肿瘤切除后的正常组织) 之间的正常组织和病变组织。

指电极 (ide), 如图 2所示, 与其他形状的电极相比, 在有限的表面上产生更大的有效传感区域。总长度的 ide 设计为860µm 检测和分析阻抗变化在不到1毫米间隔的组织, 这将提供一个高定位精度的活检和药物传递程序。总宽度的 ide 是400µm, 这是一个几何上可行的尺寸, 在曲面的皮下注射针时, 使用建议的光刻工艺。两者的间隙和宽度的 ide 是小到20µm, 这是...

Watch this Scientific Journal Video about Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications at JoVE.com

Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications

指电极的制作方法 (间隙和宽度:20 µm) 在皮下针 (直径: 720 µm) 是使用喷雾涂层和柔性膜掩在光刻过程中演示。

用光刻胶喷涂和柔性掩制备医用注射用针尖上的微细电极

We have introduced a fabrication method for electrical impedance spectroscopy (EIS)-on-a-needle (EoN: EIS-on-a-needle) to locate target tissues in the ...

Research

JoVE Journal

Neuroscience

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

突触改变老化过程中淀粉样蛋白病理研究从大鼠和转基因小鼠海马急性片的制备

The rodent hippocampal slice preparation is perhaps the most broadly used tool for investigating mammalian synaptic function and plasticity. The ...

科研

神经科学

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

使用扩频萧条的情节和慢性偏头痛的神经免疫信号建模<em在体外</em

Migraine and its transformation to chronic migraine are healthcare burdens in need of improved treatment options.  We seek to define how neural immune ...

Enabling High Grayscale Resolution Displays and Accurate Response Time Measurements on Conventional Computers

启用高灰度分辨率的显示器和传统计算机准确的响应时间测量

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments ...

Surgical Implantation of Chronic Neural Electrodes for Recording Single Unit Activity and Electrocorticographic Signals

用于记录单机活动和Electrocorticographic信号的慢性神经电极植入手术

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery.  Here we provide useful information for ...

Manufacturing and Using Piggy-back Multibarrel Electrodes for In vivo Pharmacological Manipulations of Neural Responses

Manufacturing and Using Piggy-back Multibarrel Electrodes for In vivo Pharmacological Manipulations of Neural Responses

生产和使用背驮式多管电极<em在体内</em&gt;药理手法的神经反应

In vivo recordings from single neurons allow an investigator to examine the firing properties of neurons, for example in response to sensory stimuli. ...

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

在体内双光子成像的经验依赖的分子在大脑皮质神经元的变化

The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety ...

Using Insect Electroantennogram Sensors on Autonomous Robots for Olfactory Searches

在自主机器人以昆虫触角电位传感器的嗅觉搜索

Robots designed to track chemical leaks in hazardous industrial facilities1 or explosive traces in landmine fields2 face the same problem as insects ...

Fabrication of High Contact-Density, Flat-Interface Nerve Electrodes for Recording and Stimulation Applications

高接触密度的制作，平面接口神经电极用于记录和刺激的应用

Many attempts have been made to manufacture multi-contact nerve cuff electrodes that are safe, robust and reliable for long term neuroprosthetic ...

Generation of 3-D Collagen-based Hydrogels to Analyze Axonal Growth and Behavior During Nervous System Development

生成基于3-D胶原蛋白的水凝胶,分析神经系统发育过程中的Axonal生长和行为

This protocol uses natural type I collagen to generate three-dimensional (3-D) hydrogel for monitoring and analyzing the axonal growth. The protocol is ...

Chronic Implantation of Multiple Flexible Polymer Electrode Arrays

多柔性聚合物电极阵列的慢性植入

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of ...