Name: fabrication and characterization of a conformal skin-like electronic system for quantitative, cutaneous wound management
Uploaded: 2015-09-02T14:00:00.000+00:00
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Description: Watch this Scientific Journal Video about Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management at JoVE.com

这项工作是由来自弗吉尼亚联邦大学的工程学院，以及一些电子器件制备的微细加工设施的赖特弗吉尼亚州微电子中心的启动资金支持。我们承认研究员谁作出贡献设备和临床数据（ 图3和图5本文），从公布的第 10条获得的。 W.-HY感谢服部良明的定制，数据记录软件。

该实验为器件制造，皮肤贴合，和表征示于图1，图2和4涉及两个志愿者，所有弗吉尼亚联邦学报（VCU），里士满，弗吉尼亚州，美国在生物接口纳米工程实验室完成。这项研究被批准为VCU机构审查委员会（协议号为:HM20001454），并随后从VCU人类研究的研究指导原则。批准的机构审查委员会，西北大学，芝加哥，伊利诺伊，美国:（STU69718号）在图3和图5所示的装置和临床数据是从哪里被该协议下进行对患者的实验中发表的文章10获得。 1.设备制造 注 :图2给出的示意图的整体制造工艺。 <ol><li>制备载体衬底<ol><li>通过使用金刚石刀切割一个裸3中的硅（Si）晶片放入电子设备的期望的尺寸。 注:约半数硅晶片给出了伤口设备的理想尺寸。 </li><li>脱脂Si晶片用丙酮和异丙醇（IPA）。冲洗晶片，用去离子（DI）水，然后用氮气干燥和脱水在热板上在110℃下3分钟。 </li><li>准备11个克用10聚二甲基硅氧烷（PDMS）混合物的:碱1体积比和固化剂，并在真空室中一小时脱气混合物。 注:PDMS被用于干花样检索和微制造，这是优选的湿化学（丙酮）从以前的研究为基础的7方法后转移印花。 </li><li>旋涂5克的晶片上的混合的PDMS溶液在3,000rpm下离心1分钟，完全固化在热板上在150℃下进行30分钟。 </li></ol></li><li>存款材料和模式电子<ol><li>对待PDMS-C用紫外（UV）oated晶片/臭氧通过使用UV灯（8.9毫瓦/厘米2）下3分钟，以使表面亲水性的。 注:亲水性表面提供的PDMS上的附加层均匀的涂层。 </li><li>旋涂聚酰亚胺（PI; 2毫升）上涂覆的晶片，通过移液，在4,000rpm下1分钟，从而形成在电炉上一个1.2-μm厚的层，预烘焙，在150℃下进行5分钟的PDMS，和后烘烤，在250℃进行2小时。 </li><li>存款铬（Cr），以形成一个20nm厚层，然后沉积铜（Cu），以形成一个3微米厚的层通过使用电子束（e-束）蒸发（基础压力:〜1×10 -7乇 ，沉积压力:〜1×10 -6乇，淀积速率:1 - 5 A / S）。监测薄膜厚度通过嵌入在蒸发器中的沉积控制器接口。 注:本厚厚的一层铜提供有关设备和薄Cr层的微型电阻足够的水平电导率是用来促进PI和铜之间的粘合。 </li><li>旋涂光致抗蚀剂（2ml）中的三个步骤以900rpm，10秒，1100转60秒，并以4,000rpm进行20秒，然后固化它在热板上在75℃下进行30分钟。 注意:上述的顺序步骤被用于沉积厚（&gt; 10微米）光刻胶。 </li><li>对齐的Cu电子型态（传感器;分形"的Peano&#39;设计与35微米​​的宽度和互连;蛇纹石网眼设计与50微米的宽度）通过使用UV对准在硅晶片的中心（功率:10毫瓦/秒）与曝光时间25秒。 注意:分形结构是用来提供优异的机械伸缩性，相比于仅仅蛇行特征 14。 </li><li>开发光刻胶在稀释的基础开发:一分钟（1 2比开发商和去离子水），冲洗去离子水，并用氮气干燥。检查用微型图案（铜分形和互连）范围，以确认该特征尺寸和发现任何缺陷从微粒。 注:如果有任何不想要的缺陷，然后用丙酮/ IPA / DI水漂洗去除光致抗蚀剂。用氮气干燥后，重复上述步骤，从1.2.4到1.2.6。 </li><li>通过浸渍在湿化学蚀刻剂〜6分钟蚀刻Cu层的Si晶片上（10毫升，过硫酸铵和水以1比的混合物:4;蚀刻为8nm /秒的速率在40℃），漂洗用DI水，并用氮气干燥。检查用显微镜为任何过度蚀刻图案的图案。 注意:如果图案被过度蚀刻，则可能引起的特征，这可能导致机械断裂期间设备处理和洗涤过程不希望的尖锐边缘。现有的测试结果表明，以上〜20％的过蚀刻的原始图案而引起的上述问题。 </li><li>蚀刻Cr层用反应离子蚀刻（RIE;压力:300毫乇，功率:200瓦，CF 4气体 :5秒立方厘米，O 2气:10 sccm）的5分钟。检查模式。 注:对于Cr层的蚀刻，RIE工艺优选润湿化学蚀刻，导致与铜层不利反应。 </li><li>通过浸渍于丙酮晶片（10毫升），异丙醇（10毫升），DI水（20毫升）中，除去在所述金属层上的光致抗蚀剂仍分别。然后，用氮气干燥。 </li><li>旋涂的PI（2毫升）中的金属沉积晶片上，通过移液，在4000rpm下1分钟，以形成在电炉上一个1.2-μm厚的层，预烘焙，在150℃下进行5分钟，和后烘烤处250℃下进行2小时。 </li><li>旋涂光致抗蚀剂（2ml）中的三个步骤以900rpm，10秒，1100转60秒，并以4,000rpm进行20秒，然后固化它在热板上在75℃下进行30分钟。 </li><li>对齐PI模式封装铜电子（传感器;分形"皮亚诺"的设计与35微米​​的宽度和互连;蛇纹网眼设计，250微米的宽度）与预定义的铜分形和互连通过使用UV对准器（功率:10毫瓦/秒）与曝光时间25秒。 </li><li>开发该光刻胶用稀释的显影剂（1:2的比例显影剂和DI水的）一分钟，冲洗去离子水，并用氮气干燥。检查用显微镜确认的特征尺寸和发现任何缺陷从颗粒的图案。 注:如果有任何不想要的缺陷，然后用丙酮/ IPA / DI水漂洗去除光致抗蚀剂。用氮气干燥后，重复上述步骤，从1.2.10到1.2.13。 </li><li>蚀刻的PI层用RIE（压力:170毫乇，功率:150瓦，O 2气:20 sccm）的25分钟。检查模式。 </li><li>通过浸渍于丙酮晶片（10毫升），异丙醇（10毫升），DI水（20毫升）中，除去光致抗蚀剂仍分别。然后，用氮气干燥。 </li></ol></li><li>准备一个弹性膜片<ol><li>准备将10g封装硅胶混合物（1:基料和固化剂的1体积比），并添加一个黑色油墨15有一至一体积比，这是为了便于在使用红外照相机的皮肤温度变化的控制的测量。 注:利用硅胶（透明封装胶）为低粘度，光学透明度，和电气隔离/保护的独特的特点的设备16。 </li><li>在培养皿中在150rpm，1分钟旋涂8克的混合物，以形成500微米厚的弹性膜片和固化在RT O / N。 注:该材料需要放置在平坦表面上为均匀的厚度。 </li><li>通过使用锋利的刀片切割膜成70毫米×30毫米的期望的尺寸和从培养皿轻轻分离。 </li></ol></li><li>检索和传递电子<ol><li>切的水溶性胶带（25毫米×80毫米），并轻轻地层压到所制造的电子型态，并将其放置在热板上在130℃下3分钟。 注:温度升高扩大的PDMS层的Si晶片上，以帮助从所述表面上的电子型态的离解。 </li><li>从PDMS /硅片迅速取下胶带检索电子模式。 </li><li>沉积20nm厚的Cr（粘合），后跟一个50纳米厚的二氧化硅（SiO 2）上检索的模式由电子束蒸发。 </li><li>通过使用对目标硅油膜的紫外线灯（365纳米，8.9毫瓦/厘米2）进行2分钟，以活化表面处理的UV /臭氧。 </li><li>通过将检索的模式在磁带上，以所需的位置并均匀地加入从型态的顶侧压力下降到该衬底转移该图案至硅膜。适用的水以溶解在磁带5分钟。 注:材料转移的所描述的方法是通过共价键合（的Si-O-Si）的促进沉积的二氧化硅和紫外线活化硅酮基材17之间</s向上&gt;。 </li><li>剥离胶带，冲洗用DI水，并干燥在热板上在90℃下1分钟。 </li></ol></li><li>使用有机硅膜封装装置<ol><li>准备一个10克封装硅胶混合物（1:基地1体积比和固化剂）。 </li><li>覆盖电缆接触垫具有矩形的PDMS片（22×6×1毫米3）通过范德华键合与底硅油膜，避免硅氧烷涂覆垫。 </li><li>旋涂的5克聚硅氧烷混合物的在4,000rpm下1分钟，以形成一个5微米厚层上的转移电子，然后固化在RT O / N。 </li></ol></li><li>连接一个灵活的带状电缆进行数据采集<ol><li>适用钢液通量（0.5毫升）中，通过移液，在连接器焊盘，持续3秒，使清洁表面。 </li><li>与高温压力结合的接触点柔软的细带状电缆（&gt; 60℃）。一个典型的头发straightene- [R提供易于处理和粘接。 注意:微薄膜电缆优选的常规硬线焊接，以避免对硅氧烷的转印金属膜的任何机械断裂。 </li><li>检查使用数字万用表的电连接。电阻值预计小于1欧姆的传感器垫的一端与薄膜电缆的另一端之间（距离:约1cm间隔）。 </li><li>粘结带状电缆的另一端连接到定制的印刷电路板与在步骤1.6.2中描述的相同的策略。 </li><li>检查使用数字万用表的电连接。 </li><li>通过在PCB上焊接的常规导线连接设备和数据采集硬件。 </li></ol></li></ol> 2.临床试验<ol><li>用消毒液清洁设备<ol><li>制备205克的稀释的消毒剂溶液（40:水和溶液1体积比）。 </li><li>喷溶液（10克）的设备上，并浸泡10分钟。 注:将稀释的消毒清洁剂可以储存在室温。 </li><li>用清水冲洗三次，并用干净的组织擦干。 </li></ol></li><li>建立了一系列的设备进行设备测试<ol><li>准备并与电流源，一个多路转换器，并且安装了一个膝上型计算机用于数据记录上的定制软件连接一个锁定放大器。 </li><li>将红外相机三脚架和重点热熔作为参考目标对象上。 </li><li>一个锁定放大器的设置系统参数来测量热导率（频率:1和3赫兹;时间常数:3和1秒;灵敏度:1毫伏;动态储备:高储备）和温度（频率:997赫兹;时间常数:300毫秒;灵敏度:2 mV的;动态准备金:低噪音）的应用恒定电流（2 mA）的。 </li><li>连接两个卷绕设备，备微细加工和转移印花装在伤口，对侧网站，到多路复用器从患者记录数据之前。 </li></ol></li><li>记录温度和热导率 注:数据采集软件都是定制的，它可以远程控制的锁相放大器进行实时数据监控和保存。在温度测量中，每个数据点测定每300毫秒持续20秒。该组的第10秒和接下来的10秒的数据的用于计算的平均温度值和标准差，分别。然后，记录的数据被保存为一个逗号分隔值文件，它是用来绘制一个曲线图，与红外热成像数据进行比较。在热导率的测量中，3Ω信号直接从硬件屏幕（放大器），然后将其用于计算热传导率解析读取。 <ol><li>轻轻擦上使用的防腐剂酒精对皮肤的设备应用程序的网站湿巾10。 </li><li> 2.3.2）层叠所期望的皮肤的位置由设备轻轻按压到皮肤用手指便于软粘接两个设备:一个在外科手术伤口部位，另一对侧的位置作为参考。 </li><li>通过启动数据采集测量电电压（3Ω），相关的热导率，该设备的。 </li><li>评价所获得的数据，以验证设备到皮肤的共形接触;异常值（&lt;0.1W / mK）以下示出了该装置的接触不良。 </li><li>测量的电阻通过自定义软件确定温度分布和记录数据。 </li><li>取的在皮肤上的两个装置的光学和红外图像。 </li><li>从红外图像从伤口设备（2.3.5）记录的数据进行比较的温度值。添加这两个值以自定义电子表格单独列。 </li></ol></li><li>分析所记录的数据<ol><li>导出所记录的数据传送到定制模板自动计算温度和热导率从传感器在设备的阵列。 </li><li>绘制数据（温度，并根据在不同的时间尺度，传感器位置的热导率）进行比较一个月以上的场（四组数据的第1天，3，15，和30）。 </li><li>通过比较一系列温度和根据时间的热导率数据的分析数据;突然高程值或删除告诉伤口愈合期和/或意外的异常对伤口部位的变化。 </li></ol></li></ol>

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The authors declare that they have no competing financial interests.

This article highlights the methods and protocols to fabricate a conformal, skin-like electronics system that enables conformal lamination near the wound tissues, which offers quantitative measurement of skin temperature and thermal conductivity mapping on the skin. 
The key features include the utilization of novel techniques of materials transfer printing and hard-soft materials integration to design and develop the flexible/stretchable, soft electronic device. The use of biocompatible, electrically safe, silicone layers that completely enclose the device allows the electronics to be used for the first time in a realistic clinical setting, cutaneous wound management on patients. 
In the protocol of device preparation, the following steps are critical to enhance the fabrication yield. Wet chemical etching of the metal layer (Cu) in the device should involve extreme time control since the etching rate is faster than other metals. The major drawback of Cu over-etching is the change of the combined electrical resistance of the device, which requires additional optimization and adjustment of equipment parameters in the data acquisition system. It should be noted that multiple layers of a water soluble tape needs to be used to avoid fracture during retrieval process of the electronics dissociated from a carrying PDMS. After the transfer printing of electronics with a water soluble tape, it is very important to completely remove any residue from the dissolvable material (polyvinyl alcohol) using multiple rinsing with DI water. In the process of cable bonding to the device, extra caution is required since the device is on a highly compliant and bendable material (low-modulus silicone), while the cable is thin plastic. Thus, careless handling of the device may lead to cause fracture or plastic deformation of metal resistors.
The device characterization and evaluation reveals some limitations in the clinical use. The data acquisition process using a thin cable still requires the connection with a series of equipment, which hinders continuous, long-term recording of skin parameters, relevant to wound management. The measured electrical signals accompany the downstream analysis for diagnosis, which limits on-site/point-of-care use of the device and system. 
Further improvements of the electronic system include the development of the integration of a wireless power supply and telecommunication system with the device and smart-app interface that monitors the skin parameters, collects the data, and diagnoses automatically for alerting to medical personnel. 
In conclusion, new strategies and methods of mechanical analysis and materials processing present a class of technology to develop a conformal, skin-like electronic system for quantitative, cutaneous wound management on patients. The biocompatible, waterproof, easy-to-use, mechanically compliant device provides the functions and characteristics for the use in the clinical settings. This type of electronic system has a potential to address important issues in chronic wound management.

在临床研究和生物医学研究，监测伤口愈合的已集中在基于在伤口1,2-组织形态变化的组织学评价的侵入性方法。近日，在电子技术的迅速进步使高精度成像和分析工具，可以通过数字成像3,4或共聚焦扫描显微镜和能谱4,5目视检查伤口愈合过程的发展。然而，这些成像方法需要成本高的，复杂的光学工具和操作，以及更重要的是，患者需要在测试期间，固定。因此，需要一种新的设备和系统，是定量的，非侵入性的，易于使用，价格低廉，而且多官能，提供更准确的伤口处理。 这里，介绍一种皮肤状的电子系统，该系统提供了精确，实时的温度和热condu映射及Ca2 +提供加热伤口部位的通过设备非侵入性的保形层压一个精确的水平。此装置呈现类表皮6-9的技术，皮肤安装表皮电子系统被设计为匹配到机械和材料性质（总厚度，弯曲硬度，有效模量，和质量密度）的。 该装置设计在生物相容性，皮肤友好，防水，和可重复使用的形式，可以清洗和消毒为对患者10的临床应用。安装在靠近伤口组织共形电子设备捕获炎症相（伤口愈合过程中的一个），引起血流增加，并酶促反应到伤口11,12，通过温度8和热导率13定量记录，相关的水合。实验和计算研究，确定一个最佳的力学设计，以accommod吃自然运动和施加应变而不断裂机械和捕获拉伸皮肤状的电子设备，层压共形地在皮肤表面上，这提供了获得的高保真信号的力学的基本物理。 本文中描述的方案提出的微细加工的方法的皮肤状的电子系统，测试制剂包括设备清洗，设备安装在临床环境中，并且对温度和热导率对皮肤伤口定量监测临床应用。

<table><tbody><tr><td>3&quot; Silicon wafer</td><td>University Wafer, USA</td><td></td><td>Use as carrier to fabricate the device</td></tr><tr><td>Acetone</td><td>Fisher Scientific, USA</td><td>A18-1</td><td>Use to clean a wafer and to remove photoresist</td></tr><tr><td>Isopropanol (IPA)</td><td>Fisher Scientific, USA</td><td>A459-1</td><td>Use to clean a wafer</td></tr><tr><td>AZ4620 photoresist</td><td>AZ Electrionic Materials, USA</td><td></td><td>Use to make patterns on metals and polymers</td></tr><tr><td>AZ400K developer</td><td>AZ Electrionic Materials, USA</td><td></td><td>Use to develop AZ4620 photoresist</td></tr><tr><td>Chromium etchant</td><td>Transene, USA</td><td>1020AC</td><td>Use to etch Cr layer of device</td></tr><tr><td>Copper etchant</td><td>Transene, USA</td><td>ASP-100</td><td>Use to etch Cu layer of device</td></tr><tr><td>Sylgard 184 Silicone Elastomer Kit (PDMS)</td><td>Dow Corning, USA</td><td>39100000</td><td>Use as a substrate for &#039;dry&#039; retrieval</td></tr><tr><td>PI2545 polyimide</td><td>HD MicroSystem, USA</td><td></td><td>Use to encapsulate metal layer</td></tr><tr><td>Solaris</td><td>Smooth-On, USA</td><td></td><td>Use as substrate and to encapsulate device</td></tr><tr><td>Petridish</td><td>Carolina, USA</td><td>741255</td><td>Use as mold to make substrate</td></tr><tr><td>Water-Soluble Wave Solder Tape 5414</td><td>3M, USA</td><td>AM000000217</td><td>Use to retrive device from PDMS layer</td></tr><tr><td>High Activity Liquid Stainless Steel Flux</td><td>Worthington, USA</td><td>331929</td><td>Use to remove oxidation layer on Cu</td></tr><tr><td>Flexible, micro-film cable</td><td>Elform, USA</td><td></td><td>Use to make the electrical connection between the electronic device and the data acquisition system</td></tr><tr><td>pH Neutral Cleaner</td><td>Australian Gold, USA</td><td></td><td>Use as disinfectant solution to clean device in clinical testing</td></tr><tr><td>Solder</td><td>Kester, USA</td><td>24-6337-9703</td><td>Use as material to solder hard wires</td></tr><tr><td>Ultraviolet lamp</td><td>Cole-Parmer, USA</td><td>97600-00</td><td>Use to activate PDMS layer as hydrophilic surface</td></tr><tr><td>Multiplexer</td><td>FixYourBoard, USA</td><td>U802</td><td>Use to acquire measurements from six sensing components&amp;nbsp;</td></tr><tr><td>DC/AC current source</td><td>Keithley, USA</td><td>6221</td><td>Use to supply current</td></tr><tr><td>SMD Digital Hot Air Rework Station</td><td>Aoyue, China</td><td>968A+</td><td>Use to solder hard wires, to electrically connect between the device and external instruments</td></tr><tr><td>Infrared camera</td><td>FLIR, USA</td><td>435-0001-01-00</td><td>Use to take infrared images in experiment</td></tr><tr><td>Digital multimeter</td><td>Fluke, USA</td><td>117</td><td>Use to check electrical connection</td></tr><tr><td>Lock-in amplifier</td><td>Stanford Research System, USA</td><td>SR830</td><td>Use to perform four-point-probe-measurement</td></tr><tr><td>Electron beam evaporator</td><td>9 scale Vacuum Products, USA</td><td></td><td>Use to deposit thin films (Cu and SiO&lt;sub&gt;2&lt;/sub&gt;)</td></tr></tbody></table>

fabrication and characterization of a conformal skin-like electronic system for quantitative, cutaneous wound management

Recent advances in the development of electronic technologies and biomedical devices offer opportunities for non-invasive, quantitative assessment of cutaneous wound healing on the skin. Existing methods, however, still rely on visual inspections through various microscopic tools and devices that normally include high-cost, sophisticated systems and require well trained personnel for operation and data analysis. Here, we describe methods and protocols to fabricate a conformal, skin-like electronics system that enables conformal lamination to the skin surface near the wound tissues, which provides recording of high fidelity electrical signals such as skin temperature and thermal conductivity. The methods of device fabrication provide details of step-by-step preparation of the microelectronic system that is completely enclosed with elastomeric silicone materials to offer electrical isolation. The experimental study presents multifunctional, biocompatible, waterproof, reusable, and flexible/stretchable characteristics of the device for clinical applications. Protocols of clinical testing provide an overview and sequential process of cleaning, testing setup, system operation, and data acquisition with the skin-like electronics, gently mounted on hypersensitive, cutaneous wound and contralateral tissues on patients.

图1表示的该共形，皮样的电子系统的特性，设计用于患者的定量，皮肤伤口管理的概述。多功能电子装置由微观分形结构3,14和丝状蛇形走线9,17上形成薄的弹性膜，它具有优越的机械拉伸和弯曲。它是完全由硅层所包围的兼容装置能够平缓，可逆层压上通过单独范德华相互作用的皮肤。该设备的独特特征包括生物相容性，防水性，易于使用，并机械灵活性在现实的临床环境中使用。 混合材料如聚合物和金属（聚硅氧烷，聚酰亚胺和铜）的积分产生的电安全，防水，和生物相容设备（图2A）。分形阵列（铜;铜）的电阻（35微米的宽度和厚度为3微米）被放置在中性机械平面，由封闭的聚酰亚胺（PI，1.2微米厚）的层，以尽量减少对芯施加弯曲应变在临床应用中的材料（铜）。 上的硅膜的装置的总厚度仅为〜600微米，通过提供极端弯曲加工性。在图2B的示意图描述的皮肤状的电子系统的微细加工。的制造方法结合了传统的微细加工技术（金属化，光刻和蚀刻）与新开发的转印印刷技术（检索，转移和粘合）9,14,18,19。这种类型的装置的可通过使用大规模转移印花用自动印刷设备20,21进行放大。 图3总结了力学升拉伸性和皮肤状电子电功能性，报告了在现有的工作10。力学和材料研究通过有限元法（FEM）提供最佳的系统设计，以适应自然运动和施加的菌株，参与临床使用，没有机械断裂（图3A，上图）。实验研究呈现的分形结构与拉伸应变高达30％（图3AA，底部）的机械性能显示与FEM结果非常吻合。与微尺度电阻装置用于温度和热导率，并提供精确的，局部加热的定量测量（ 图3B - 3D）。通过使用红外相机和高灵敏度的热板（图3B）获得的根据温度变化的电阻的校准曲线。所测量的热导率的评价方法是适于从使用3欧米加电压信号在两个不同的交流电流的频率（ 图3c）的3欧米加技术13。施加电流（35毫安的10毫瓦）到分形电阻器发生的焦耳热，它提供可控温度的致动在治疗模式（图3D）。 对于实际的，临床应用中，手持式装置的建议的清洗过程涉及到对患者使用前消毒。喷涂的防水装置上的消毒液和后续漂洗水中三次准备装置，用于临床试验（ 图4A和4B）。该装置的定性生物相容性的评估使用数字接触显微镜目视检查皮肤表面（图4C），文中对皮肤的颜色和纹理过使用对患者多次循环的变化。一个红外（IR）thermogr​​apHY可以使皮肤条件大约两个星期（图4D）的定量评估，因为副作用如红斑导致升温22。所检查的器件被层叠伤口附近的组织和对侧位置（作为参考）。温度和热导率的相关参数的记录是利用一个数据采集系统和红外成像在诊疗室（图4E和4F）进行。 图5示从之前的研究10的患者的皮肤伤口愈合定量测定的代表性数据。一系列的图 5A中示出的照片伤口愈合与皮肤的车载装置一个月以上的过程中的监视处理。染成与黑色墨水卷绕装置层压邻近手术伤口。笔上引导装置安装在相同的位置进行定量的DAT皮肤痕<html>从1天至30的温度和热导率变动的测量天用在设备和比较伤口和参考点之间的传感器阵列的比较捕获的伤口愈合阶段，炎症（ 图5B - 5E）。高度敏感的，六在伤口设备传感器能够捕捉的体温和点强烈炎症第3天（ 图5B - 5C）最小变化率和热导率（图5D - 5E）的记录的变化。一组参考数据是从对侧作为对照测定。 <img alt="图1" src="/files/ftp_upload/53037/53037fig1.jpg" /> 图上的患者皮肤状，伤口监视装置的特征1.概述。&gt;点击此处查看该图的放大版本。 <img alt="图2" src="/files/ftp_upload/53037/53037fig2.jpg" /> 图2.设备制造（A）的示意图的设备布局（左侧的图示;层1:透明硅的顶部，层2:PI，层3:铜，层4:PI和层5:黑色硅酮处底部），完成后，灵活/拉伸电子（右）。（B）插图的一步一步的制造工艺（横截面图）的。 <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53037/53037fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图3" src="/files/ftp_upload/53037/53037fig3.jpg" /> 图3.设备特性（转载自许可 <e米&gt;高级医疗材料，3（10），1597至1607年，2014年）10。（A）的有限元法（FEM）的结果（上）和一个分形结构的单轴拉伸应变达到了相应的实验结果（底）的30％。（B）的温度下使用六个传感器用于设备校准的测量。（C）的测量使用三个传感器，用于设备校准的热导率。（D）中被用作一个微型加热器与局部焦耳加热设备的红外热。 <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53037/53037fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图4" src="/files/ftp_upload/53037/53037fig4.jpg" /> 图4.临床试验过程。 （A）使用的消毒清洗液的装置。（B）与水冲洗来清洁表面，用于临床试验。使用数字接触显微镜（左）和皮肤（右）的放大视图（C）的皮肤评估。（D）中的皮肤温度的定量评估红外热的变化。（E）用于伤口处理在检查室的临床设置。（F）的伤口（右腿）和对侧的网站（左腿）组织附近的层压设备的放大照片。 <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53037/53037fig4large.jpg" target="_blank">请点击此处查看这是一个更大的版本数字。</a> <img alt="图5" src="/files/ftp_upload/53037/53037fig5.jpg" /> 伤口愈合与设备量化管理的图5。代表性的数据（再现与先进的医疗资料的申请 </eM&gt;，3（10），1597年至1607年，26年）10。（A）图片与设备在一个月的过程中，伤口。（二）记录在伤口附近的温度分布的一个月，在六个传感器设备（插图）。在一对侧位置作为基准温度分布（℃）记录 。一个月伤口与三个传感器中的装置（插图）附近的热导率（D）的记录。热（E）的记录电导率在对侧定位作为参考。 <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53037/53037fig5large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

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Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management

This article presents methods to fabricate and characterize a conformal, skin-like electronic system and protocols for the use in clinical applications, particularly on cutaneous wound management.

制作定量，皮肤伤口管理一个形皮肤般的电子系统与表征

Recent advances in the development of electronic technologies and biomedical devices offer opportunities for non-invasive, quantitative assessment of ...

fabrication-characterization-conformal-skin-like-electronic-system

Universidad San Sebastian

Research

JoVE Journal

Bioengineering

8.8K 次观看.  Virginia Commonwealth University. This article presents methods to fabricate and characterize a conformal, skin-like electronic system and protocols for the use in clinical applications, particularly on cutaneous wound management. 

视频: Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management

Dual-mode Imaging of Cutaneous Tissue Oxygenation and Vascular Function

Accurate assessment of cutaneous tissue oxygenation and vascular function is important for appropriate detection, staging, and treatment of many health disorders such as chronic wounds. We report the development of a dual-mode imaging system for non-invasive and non-contact imaging of cutaneous tissue oxygenation and vascular function. The imaging system integrated an infrared camera, a CCD camera, a liquid crystal tunable filter and a high intensity fiber light source. A Labview interface was programmed for equipment control, synchronization, image acquisition, processing, and visualization. Multispectral images captured by the CCD camera were used to reconstruct the tissue oxygenation map. Dynamic thermographic images captured by the infrared camera were used to reconstruct the vascular function map. Cutaneous tissue oxygenation and vascular function images were co-registered through fiduciary markers. The performance characteristics of the dual-mode image system were tested in humans.

A dual-mode imaging system was developed for non-contact assessment of cutaneous tissue oxygenation and vascular function.

双模式成像，皮肤组织氧合和血管功能

Accurate assessment of cutaneous tissue oxygenation and vascular function is important for appropriate detection, staging, and treatment of many health ...

科研

医学

A Simplified Technique for Producing an Ischemic Wound Model

One major obstacle in current diabetic wound research is a lack of an ischemic wound model that can be safely used in diabetic animals. Drugs that work well in non-ischemic wounds may not work in human diabetic wounds because vasculopathy is one major factor that hinders healing of these wounds. We published an article in 2007 describing a rabbit ear ischemic wound model created by a minimally invasive surgical technique. Since then, we have further simplified the procedure for easier operation. On one ear, three small skin incisions were made on the vascular pedicles, 1-2 cm from the ear base. The central artery was ligated and cut along with the nerve. The whole cranial bundle was cut and ligated, leaving only the caudal branch intact. A circumferential subcutaneous tunnel was made through the incisions, to cut subcutaneous tissues, muscles, nerves, and small vessels. The other ear was used as a non-ischemic control. Four wounds were made on the ventral side of each ear. This technique produces 4 ischemic wounds and 4 non-ischemic wounds in one animal for paired comparisons. After surgery, the ischemic ear was cool and cyanotic, and showed reduced movement and a lack of pulse in the ear artery. Skin temperature of the ischemic ear was 1-10 &deg;C lower than that on the normal ear and this difference was maintained for more than one month. Ear tissue high-energy phosphate contents were lower in the ischemic ear than the control ear. Wound healing times were longer in the ischemic ear than in the non-ischemic ear when the same treatment was used. The technique has now been used on more than 80 rabbits in which 23 were diabetic (diabetes time ranging from 2 weeks to 2 years). No single rabbit has developed any surgical complications such as bleeding, infection, or rupture in the skin incisions. The model has many advantages, such as little skin disruption, longer ischemic time, and higher success rate, when compared to many other models. It can be safely used in animals with reduced resistance, and can also be modified to meet different testing requirements.

We have developed a minimally invasive technique to create a rabbit ischemic ear wound model by dividing the central artery and nerve and the cranial neurovascular bundle. A subcutaneous tunnel then cuts all subcutaneous tissues. This procedure causes minimal skin disruption and can be safely used in diabetic animals.

一个生产缺血性损伤模型的简化技术

One major obstacle in current diabetic wound research is a lack of an ischemic wound model that can be safely used in diabetic animals. Drugs that work ...

Generation of a Three-dimensional Full Thickness Skin Equivalent and Automated Wounding

In vitro models are a cost effective and ethical alternative to study cutaneous wound healing processes. Moreover, by using human cells, these models reflect the human wound situation better than animal models. Although two-dimensional models are widely used to investigate processes such as cellular migration and proliferation, models that are more complex are required to gain a deeper knowledge about wound healing. Besides a suitable model system, the generation of precise and reproducible wounds is crucial to ensure comparable results between different test runs. In this study, the generation of a three-dimensional full thickness skin equivalent to study wound healing is shown. The dermal part of the models is comprised of human dermal fibroblast embedded in a rat-tail collagen type I hydrogel. Following the inoculation with human epidermal keratinocytes and consequent culture at the air-liquid interface, a multilayered epidermis is formed on top of the models. To study the wound healing process, we additionally developed an automated wounding device, which generates standardized wounds in a sterile atmosphere.

The goal of this protocol is to build up a three-dimensional full thickness skin equivalent, which resembles natural skin. With a specifically constructed automated wounding device, precise and reproducible wounds can be generated under maintenance of sterility.

三维全层皮肤的生成等效和自动伤人

In vitro models are a cost effective and ethical alternative to study cutaneous wound healing processes. Moreover, by using human cells, these models ...

生物工程

A Simple and Scalable Fabrication Method for Organic Electronic Devices on Textiles

Today, wearable electronics devices combine a large variety of functional, stretchable, and flexible technologies. However, in many cases, these devices cannot be worn under everyday conditions. Therefore, textiles are commonly considered the best substrate to accommodate electronic devices in wearable use. In this paper, we describe how to selectively pattern organic electroactive materials on textiles from a solution in an easy and scalable manner. This versatile deposition technique enables the fabrication of wearable organic electronic devices on clothes.

In this paper, we present a protocol to selectively deposit organic materials on textiles, which allows for the direct integration of organic electronic devices with wearables. The fabricated devices can be fully integrated in textiles, respecting their mechanical appearance and enabling sensing capabilities.

关于纺织品有机电子设备的简单和可扩展的制作方法

Today, wearable electronics devices combine a large variety of functional, stretchable, and flexible technologies. However, in many cases, these devices ...

Human Ex vivo Wound Model and Whole-Mount Staining Approach to Accurately Evaluate Skin Repair

Chronic non-healing wounds, which primarily affect the elderly and diabetic, are a significant area of clinical unmet need. Unfortunately, current chronic wound treatments are inadequate, while available pre-clinical models poorly predict the clinical efficacy of new therapies. Here we describe a high throughput, pre-clinical model to assess multiple aspects of the human skin repair response. Partial thickness wounds were created in human ex vivo skin and cultured across a healing time course. Skin wound biopsies were collected in fixative for the whole-mount staining procedure. Fixed samples were blocked and incubated in primary antibody, with detection achieved via fluorescently conjugated secondary antibody. Wounds were counterstained and imaged via confocal microscopy before calculating percentage wound closure (re-epithelialization) in each biopsy. Applying this protocol, we reveal that 2 mm excisional wounds created in healthy donor skin are fully re-epithelialized by day 4-5 post-wounding. On the contrary, closure rates of diabetic skin wounds are significantly reduced, accompanied by perturbed barrier reformation. Combining human skin wounding with a novel whole-mount staining approach allows a rapid and reproducible method to quantify ex vivo wound repair. Collectively, this protocol provides a valuable human platform to evaluate the effectiveness of potential wound therapies, transforming pre-clinical testing and validation.

Here we demonstrate an optimized technique for assessing wound repair using ex vivo human skin combined with a whole-mount staining approach. This methodology provides a pre-clinical platform for the evaluation of potential wound therapies.

人体外伤模型和全山染色方法，以准确评估皮肤修复

Chronic non-healing wounds, which primarily affect the elderly and diabetic, are a significant area of clinical unmet need. Unfortunately, current chronic ...

发育生物学

Generation of Self-assembled Vascularized Human Skin Equivalents

Human skin equivalents (HSEs) are tissue engineered constructs that model epidermal and dermal components of human skin. These models have been used to study skin development, wound healing, and grafting techniques. Many HSEs continue to lack vasculature and are additionally analyzed through post-culture histological sectioning which limits volumetric assessment of the structure. Presented here is a straightforward protocol utilizing accessible materials to generate vascularized human skin equivalents (VHSE); further described are volumetric imaging and quantification techniques of these constructs. Briefly, VHSEs are constructed in 12 well culture inserts in which dermal and epidermal cells are seeded into rat tail collagen type I gel. The dermal compartment is made up of fibroblast and endothelial cells dispersed throughout collagen gel. The epidermal compartment is made up of keratinocytes (skin epithelial cells) that differentiate at the air-liquid interface. Importantly, these methods are customizable based on needs of the researcher, with results demonstrating VHSE generation with two different fibroblast cell types: human dermal fibroblasts (hDF) and human lung fibroblasts (IMR90s). VHSEs were developed, imaged through confocal microscopy, and volumetrically analyzed using computational software at 4- and 8-week timepoints. An optimized process to fix, stain, image, and clear VHSEs for volumetric examination is described. This comprehensive model, imaging, and analysis techniques are readily customizable to the specific research needs of individual labs with or without prior HSE experience.

The goal of this protocol is to describe the generation and volumetric analysis of vascularized human skin equivalents using accessible and simple techniques for long term culture. To the extent possible, the rationale for steps is described to allow researchers the ability to customize based on their research needs.

自组装血管化人体皮肤等价物的生成

Human skin equivalents (HSEs) are tissue engineered constructs that model epidermal and dermal components of human skin. These models have been used to ...

Generation of a Simplified Three-Dimensional Skin-on-a-chip Model in a Micromachined Microfluidic Platform

This work presents a new, cost-effective, and reliable microfluidic platform with the potential to generate complex multilayered tissues. As a proof of concept, a simplified and undifferentiated human skin containing a dermal (stromal) and an epidermal (epithelial) compartment has been modelled. To accomplish this, a versatile and robust, vinyl-based device divided into two chambers has been developed, overcoming some of the drawbacks present in microfluidic devices based on polydimethylsiloxane (PDMS) for biomedical applications, such as the use of expensive and specialized equipment or the absorption of small, hydrophobic molecules and proteins. Moreover, a new method based on parallel flow was developed, enabling the in situ deposition of both the dermal and epidermal compartments. The skin construct consists of a fibrin matrix containing human primary fibroblasts and a monolayer of immortalized keratinocytes seeded on top, which is subsequently maintained under dynamic culture conditions. This new microfluidic platform opens the possibility to model human skin diseases and extrapolate the method to generate other complex tissues.

Here, we present a protocol to generate a three-dimensional simplified and undifferentiated skin model using a micromachined microfluidic platform. A parallel flow approach allows the in situ deposition of a dermal compartment for the seeding of epithelial cells on top, all controlled by syringe pumps.

在微加工微流体平台中生成简化的三维芯片皮肤模型

This work presents a new, cost-effective, and reliable microfluidic platform with the potential to generate complex multilayered tissues. As a proof of ...

Conformable Wearable Electrodes: From Fabrication to Electrophysiological Assessment

Wearable electronic devices are becoming key players in monitoring the body signals predominantly altered during physical activity tracking. Considering the growing interest in telemedicine and personalized care driven by the rise of the Internet of Things era, wearable sensors have expanded their field of application into healthcare. To ensure the collection of clinically relevant data, these devices need to establish conformable interfaces with the human body to provide high-signal-quality recordings and long-term operation. To this end, this paper presents a method to easily fabricate conformable thin tattoo- and soft textile-based sensors for their application as wearable organic electronic devices in a broad spectrum of surface electrophysiological recordings. 
The sensors are developed through a cost-effective and scalable process of cutaneous electrode patterning using poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS), the most popular conductive polymer in bioelectronics, on off-the-shelf, wearable substrates. This paper presents key steps in electrode characterization through impedance spectroscopy to investigate their performance in signal transduction when coupled with the skin. Comparative studies are required to position the performance of novel sensors with respect to the clinical gold standard. To validate the fabricated sensors' performance, this protocol shows how to perform various biosignal recordings from different configurations through a user-friendly and portable electronic setup in a laboratory environment. This methods paper will allow multiple experimental initiatives to advance the current state of the art in wearable sensors for human body health monitoring.

Two recent technologies-tattoo and textiles-have demonstrated promising results in cutaneous sensing. Here, we present the fabrication and evaluation methods of tattoo and textile electrodes for cutaneous electrophysiological sensing. These electronic interfaces made of conductive polymers outperform the existing standards in terms of comfort and sensitivity.

适形可穿戴电极:从制造到电生理评估

Wearable electronic devices are becoming key players in monitoring the body signals predominantly altered during physical activity tracking. Considering ...

Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.

Wound healing is a complex process that requires the orderly progression of inflammation, granulation tissue formation, fibrosis, and resolution. Murine models provide valuable mechanistic insight into these processes; however, no single model fully addresses all aspects of the wound healing response. Instead, it is ideal to use multiple models to address the different aspects of wound healing. Here, two different methods that address diverse aspects of the wound healing response are described. In the first model, polyvinyl alcohol sponges are subcutaneously implanted along the mouse dorsum. Following sponge retrieval, cells can be isolated by mechanical disruption, and fluids can be extracted by centrifugation, thus allowing for a detailed characterization of cellular and cytokine responses in the acute wound environment. A limitation of this model is the inability to assess the rate of wound closure. For this, a tail skin excision model is utilized. In this model, a 10 mm x 3 mm rectangular piece of tail skin is excised along the dorsal surface, near the base of the tail. This model can be easily photographed for planimetric analysis to determine healing rates and can be excised for histological analysis. Both described methods can be utilized in genetically altered mouse strains, or in conjunction with models of comorbid conditions, such as diabetes, aging, or secondary infection, in order to elucidate wound healing mechanisms.

Here, two murine wound healing models are described, one designed to assess cellular and cytokine wound healing responses and the other to quantify the rate of wound closure. These methods can be used with complex disease models such as diabetes to determine mechanisms of various aspects of poor wound healing.

使用多盐皮下聚乙烯醇海绵植入和外向尾皮肤伤口模型进行急性伤口愈合评估。

Wound healing is a complex process that requires the orderly progression of inflammation, granulation tissue formation, fibrosis, and resolution. Murine ...

免疫与感染

开发用于生物膜感染烧伤创面研究的长期猪模型

Swine Model of Biofilm Infection and Invisible Wounds

Biofilm infection is a major contributor to wound chronicity. The establishment of clinically relevant experimental wound biofilm infection requires the involvement of the host immune system. Iterative changes in the host and pathogen during the formation of such clinically relevant biofilm can only occur in vivo. The swine wound model is recognized for its advantages as a powerful pre-clinical model. There are several reported approaches for studying wound biofilms. In vitro and ex vivo systems are deficient in terms of the host immune response. Short-term in vivo studies involve acute responses and, thus, do not allow for biofilm maturation, as is known to occur clinically. The first long-term swine wound biofilm study was reported in 2014. The study recognized that biofilm-infected wounds may close as determined by planimetry, but the skin barrier function of the affected site may fail to be restored. Later, this observation was validated clinically. The concept of functional wound closure was thus born. Wounds closed but deficient in skin barrier function may be viewed as invisible wounds. In this work, we seek to report the methodological details necessary to reproduce the long-term swine model of biofilm-infected severe burn injury, which is clinically relevant and has translational value. This protocol provides detailed guidance on establishing an 8 week wound biofilm infection using P. aeruginosa (PA01). Eight full-thickness burn wounds were created symmetrically on the dorsum of domestic white pigs, which were inoculated with (PA01) at day 3 post-burn; subsequently, noninvasive assessments of the wound healing were conducted at different time points using laser speckle imaging (LSI), high-resolution ultrasound (HUSD), and transepidermal water loss (TEWL). The inoculated burn wounds were covered with a four-layer dressing. Biofilms, as established and confirmed structurally by SEM at day 7 post-inoculation, compromised the functional wound closure. Such an adverse outcome is subject to reversal in response to appropriate interventions.

作者聚焦:研究伤口生物膜形成中的宿主-微生物相互作用 

Chronic wounds that are resistant to antibiotics are a major threat to the healthcare system. Biofilm infections are stubborn and hostile and can cause deficient functional wound closure. We report a clinically relevant swine model of biofilm-infected full-thickness chronic wounds. This model is powerful for mechanistic studies as well as for testing interventions.

猪生物膜感染和隐形伤口模型

Biofilm infection is a major contributor to wound chronicity. The establishment of clinically relevant experimental wound biofilm infection requires the ...