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>

<ol>
	<li>Dargaville, T. R., 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=Sensors+and+imaging+for+wound+healing:+A+review.">Sensors and imaging for wound healing: A review.</a> Biosens Bioelectron. 41, 30-42 (2013).</li><li>Panuncialman, J., Hammerman, S., Carson, P., Falanga, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Wound+edge+biopsy+sites+in+chronic+wounds+heal+rapidly+and+do+not+result+in+delayed+wound+healing.">Wound edge biopsy sites in chronic wounds heal rapidly and do not result in delayed wound healing.</a> J Invest Dermatol. 129, S47-S47 (2009).</li><li>Hess, C. T., Kirsner, R. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Orchestrating Wound Healing: Assessing and Preparing the Wound Bed. Adv Skin Wound Care. 16 (5), 246-257 (2003).</li><li>Lange-Asschenfeldt, S., 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=Applicability+of+confocal+laser+scanning+microscopy+for+evaluation+and+monitoring+of+cutaneous+wound+healing.">Applicability of confocal laser scanning microscopy for evaluation and monitoring of cutaneous wound healing.</a> J Biomed Opt. 17 (7), (2012).</li><li>Crane, N. J., Elster, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vibrational+spectroscopy:+a+tool+being+developed+for+the+noninvasive+monitoring+of+wound+healing.">Vibrational spectroscopy: a tool being developed for the noninvasive monitoring of wound healing.</a> J Biomed Opt. 17 (7), (2012).</li><li>Jeong, J. W., 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=Materials+and+Optimized+Designs+for+Human-Machine+Interfaces+Via+Epidermal+Electronics.">Materials and Optimized Designs for Human-Machine Interfaces Via Epidermal Electronics.</a> Adv Mater. 25 (47), 6839-6846 (2013).</li><li>Kim, D. 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=Epidermal+Electronics.">Epidermal Electronics.</a> Science. 333 (6044), 838-843 (2011).</li><li>Webb, R. 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=Ultrathin+conformal+devices+for+precise+and+continuous+thermal+characterization+of+human+skin+(vol+12,+pg+938).">Ultrathin conformal devices for precise and continuous thermal characterization of human skin (vol 12, pg 938).</a> Nat Mater. 12, 1078-1078 (2013).</li><li>Yeo, W. 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=Multifunctional+Epidermal+Electronics+Printed+Directly+Onto+the+Skin.">Multifunctional Epidermal Electronics Printed Directly Onto the Skin.</a> Adv Mater. 25 (20), 2773-2778 (2013).</li><li>Hattori, Y., 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=Multifunctional+skin-like+electronics+for+quantitative,+clinical+monitoring+of+cutaneous+wound+healing.">Multifunctional skin-like electronics for quantitative, clinical monitoring of cutaneous wound healing.</a> Adv Healthc Mater. 3 (10), 1597-1607 (2014).</li><li>Guo, S., DiPietro, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+Affecting+Wound+Healing.">Factors Affecting Wound Healing.</a> J Dent Res. 89 (3), 219-229 (2010).</li><li>Matzeu, G., 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=Skin+temperature+monitoring+by+a+wireless+sensor.">Skin temperature monitoring by a wireless sensor.</a> Ieee Ind Elec. , 3533-3535 (2011).</li><li>Cahill, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thermal-Conductivity+Measurement+from+30-K+to+750-K+-+the+3-Omega+Method.">Thermal-Conductivity Measurement from 30-K to 750-K - the 3-Omega Method.</a> Rev Sci Instrum. 61 (2), 802-808 (1990).</li><li>Fan, J. 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=Fractal+Design+Concepts+for+Stretchable+Electronics.">Fractal Design Concepts for Stretchable Electronics.</a> Nature Commun. 5 (3266), (2013).</li><li>Song, Y. 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=Digital+cameras+with+designs+inspired+by+the+arthropod+eye.">Digital cameras with designs inspired by the arthropod eye.</a> Nature. 497 (7447), 95-99 (2013).</li><li>Jeong, J. W., 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=Capacitive+Epidermal+Electronics+for+Electrically+Safe,+Long-Term+Electrophysiological+Measurements.">Capacitive Epidermal Electronics for Electrically Safe, Long-Term Electrophysiological Measurements.</a> Adv Healthc Mater. 3 (5), 642-648 (2013).</li><li>Zhang, Y. 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=Experimental+and+Theoretical+Studies+of+Serpentine+Microstructures+Bonded+To+Prestrained+Elastomers+for+Stretchable+Electronics.">Experimental and Theoretical Studies of Serpentine Microstructures Bonded To Prestrained Elastomers for Stretchable Electronics.</a> Adv Funct Mater. 24 (14), 2028-2037 (2014).</li><li>Carlson, A., Bowen, A. M., Huang, Y. G., Nuzzo, R. G., Rogers, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transfer+Printing+Techniques+for+Materials+Assembly+and+Micro/Nanodevice+Fabrication.">Transfer Printing Techniques for Materials Assembly and Micro/Nanodevice Fabrication.</a> Adv Mater. 24 (39), 5284-5318 (2012).</li><li>Yeo, W. H., Webb, R. C., Lee, W., Jung, S., Rogers, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bio-integrated+electronics+and+sensor+systems.">Bio-integrated electronics and sensor systems.</a> Proc Spie. 8725, (2013).</li><li>Chung, H. 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=Fabrication+of+Releasable+Single-Crystal+Silicon&#8211;Metal+Oxide+Field-Effect+Devices+and+Their+Deterministic+Assembly+on+Foreign+Substrates.">Fabrication of Releasable Single-Crystal Silicon&#8211;Metal Oxide Field-Effect Devices and Their Deterministic Assembly on Foreign Substrates.</a> Adv Funct Mater. 21 (16), 3029-3036 (2011).</li><li>Kim, H. S., 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=Unusual+strategies+for+using+indium+gallium+nitride+grown+on+silicon+(111)+for+solid-state+lighting.">Unusual strategies for using indium gallium nitride grown on silicon (111) for solid-state lighting.</a> Proc Natl Acad Sci U.S.A. 108 (25), 10072-10077 (2011).</li><li>Padilla-Medina, J. 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=Assessment+technique+for+acne+treatments+based+on+statistical+parameters+of+skin+thermal+images.">Assessment technique for acne treatments based on statistical parameters of skin thermal images.</a> J Biomed Opt. 19 (4), 046019-046019 (2014).</li></ol>

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, elec...

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 border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>3&#34; Silicon wafer</td>
			<td>University Wafer, USA</td>
			<td>N/A</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>N/A</td>
			<td>Use to make patterns on metals and polymers</td>
		</tr>
		<tr>
			<td>AZ400K developer</td>
			<td>AZ Electrionic Materials, USA</td>
			<td>N/A</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 &#39;dry&#39; retrieval</td>
		</tr>
		<tr>
			<td>PI2545 polyimide</td>
			<td>HD MicroSystem, USA</td>
			<td>N/A</td>
			<td>Use to encapsulate metal layer</td>
		</tr>
		<tr>
			<td>Solaris</td>
			<td>Smooth-On, USA</td>
			<td>N/A</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>N/A (customized)</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>N/A</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&#160;</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>N/A (customized)</td>
			<td>Use to deposit thin films (Cu and SiO2)</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...

Watch this Scientific Journal Video about Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management at JoVE.com

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

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

Microinjection Wound Assay and In vivo Localization of Epidermal Wound Response Reporters in Drosophila Embryos.

The Drosophila embryo develops a robust epidermal layer that serves both to protect the internal cells from a harsh external environment as well as to maintain cellular homeostasis. Puncture injury with glass needles provides a direct method to trigger a rapid epidermal wound response that activates wound transcriptional reporters, which can be visualized by a localized reporter signal in living embryos or larvae. Puncture or laser injury also provides signals that promote the recruitment of hemocytes to the wound site. Surprisingly, severe (through and through) puncture injury in late stage embryos only rarely disrupts normal embryonic development, as greater than 90% of such wounded embryos survive to adulthood when embryos are injected in an oil medium that minimizes immediate leakage of hemolymph from puncture sites. The wound procedure does require micromanipulation of the Drosophila embryos, including manual alignment of the embryos on agar plates and transfer of the aligned embryos to microscope slides. The Drosophila epidermal wound response assay provides a quick system to test the genetic requirements of a variety of biological functions that promote wound healing, as well as a way to screen for potential chemical compounds that promote wound healing. The short life cycle and easy culturing routine make Drosophila a powerful model organism. Drosophila clean wound healing appears to coordinate the epidermal regenerative response, with the innate immune response, in ways that are still under investigation, which provides an excellent system to find conserved regulatory mechanisms common to Drosophila and mammalian epidermal wounding.

Microinjection Wound Assay and In vivo Localization of Epidermal Wound Response Reporters in Drosophila Embryos.

The embryonic epidermis of very late stage Drosophila embryos provides an in vivo system for rapid puncture wound response analysis and can be combined with genetic manipulations or chemical microinjection treatments to advance studies in wound healing for translation into mammalian models.

创伤显微注射和分析<em&gt;在体内</em&gt;表皮的伤口本地化响应记者在<em&gt;果蝇</em&gt;胚胎。

The Drosophila embryo develops a robust epidermal layer that serves both to protect the internal cells from a harsh external environment as well as to ...

科研

生物工程

Microfluidic Fabrication of Polymeric and Biohybrid Fibers with Predesigned Size and Shape

A &#8220;sheath&#8221; fluid passing through a microfluidic channel at low Reynolds number can be directed around another &#8220;core&#8221; stream and used to dictate the shape as well as the diameter of a core stream.&#160;Grooves in the top and bottom of a microfluidic channel were designed to direct the sheath fluid and shape the core fluid.&#160;By matching the viscosity and hydrophilicity of the sheath and core fluids, the interfacial effects are minimized and complex fluid shapes can be formed.&#160;Controlling the relative flow rates of the sheath and core fluids determines the cross-sectional area of the core fluid.&#160;Fibers have been produced with sizes ranging from 300 nm to ~1 mm, and fiber cross-sections can be round, flat, square, or complex as in the case with double anchor fibers. Polymerization of the core fluid downstream from the shaping region solidifies the fibers.&#160;Photoinitiated click chemistries are well suited for rapid polymerization of the core fluid by irradiation with ultraviolet light.&#160;Fibers with a wide variety of shapes have been produced from a list of polymers including liquid crystals, poly(methylmethacrylate), thiol-ene and thiol-yne resins, polyethylene glycol, and hydrogel derivatives. Minimal shear during the shaping process and mild polymerization conditions also makes the fabrication process well suited for encapsulation of cells and other biological components.

Two adjacent fluids passing through a grooved microfluidic channel can be directed to form a sheath around a prepolymer core; thereby&#160;determining both shape and cross-section. Photoinitiated polymerization, such as thiol click chemistry, is well suited for rapidly solidifying the core fluid into a microfiber with predetermined size and shape.

预设计尺寸和形状的聚合物纤维和生物贿赂纤维的微流体制造

A &#8220;sheath&#8221; fluid passing through a microfluidic channel at low Reynolds number can be directed around another &#8220;core&#8221; stream and ...

Microfluidic Platform with Multiplexed Electronic Detection for Spatial Tracking of Particles

Microfluidic processing of biological samples typically involves differential manipulations of suspended particles under various force fields in order to spatially fractionate the sample based on a biological property of interest. For the resultant spatial distribution to be used as the assay readout, microfluidic devices are often subjected to microscopic analysis requiring complex instrumentation with higher cost and reduced portability. To address this limitation, we have developed an integrated electronic sensing technology for multiplexed detection of particles at different locations on a microfluidic chip. Our technology, called Microfluidic CODES, combines Resistive Pulse Sensing with Code Division Multiple Access to compress 2D spatial information into a 1D electrical signal. In this paper, we present a practical demonstration of the Microfluidic CODES technology to detect and size cultured cancer cells distributed over multiple microfluidic channels. As validated by the high-speed microscopy, our technology can accurately analyze dense cell populations all electronically without the need for an external instrument. As such, the Microfluidic CODES can potentially enable low-cost integrated lab-on-a-chip devices that are well suited for the point-of-care testing of biological samples.

We demonstrate a microfluidic platform with an integrated surface electrode network that combines resistive pulse sensing (RPS) with code division multiple access (CDMA), to multiplex detection and sizing of particles in multiple microfluidic channels.

与复用电子检测的粒子的空间跟踪微流体平台

Microfluidic processing of biological samples typically involves differential manipulations of suspended particles under various force fields in order to ...

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 ...

Fabrication and Validation of an Organ-on-chip System with Integrated Electrodes to Directly Quantify Transendothelial Electrical Resistance

Organs-on-chips, in vitro models involving the culture of (human) tissues inside microfluidic devices, are rapidly emerging and promise to provide useful research tools for studying human health and disease. To characterize the barrier function of cell layers cultured inside organ-on-chip devices, often transendothelial or transepithelial electrical resistance (TEER) is measured. To this end, electrodes are usually integrated into the chip by micromachining methods to provide more stable measurements than is achieved with manual insertion of electrodes into the inlets of the chip. However, these electrodes frequently hamper visual inspection of the studied cell layer or require expensive cleanroom processes for fabrication. To overcome these limitations, the device described here contains four easily integrated electrodes that are placed and fixed outside of the culture area, making visual inspection possible. Using these four electrodes the resistance of six measurement paths can be quantified, from which the TEER can be directly isolated, independent of the resistance of culture medium-filled microchannels. The blood-brain barrier was replicated in this device and its TEER was monitored to show the device applicability. This chip, the integrated electrodes and the TEER determination method are generally applicable in organs-on-chips, both to mimic other organs or to be incorporated into existing organ-on-chip systems.

This publication describes the fabrication of an organ-on-chip device with integrated electrodes for direct quantification of transendothelial electrical resistance (TEER). For validation, the blood-brain barrier was mimicked inside this microfluidic device and its barrier function was monitored. The presented methods for electrode integration and direct TEER quantification are generally applicable.

用集成电极直接量化 Transendothelial 电阻的 Organ-on-chip 系统的制作与验证

Organs-on-chips, in vitro models involving the culture of (human) tissues inside microfluidic devices, are rapidly emerging and promise to provide useful ...

Fabrication and Characterization of Griffithsin-modified Fiber Scaffolds for Prevention of Sexually Transmitted Infections

Electrospun fibers (EFs) have been widely used in a variety of therapeutic applications; however, they have only recently been applied as a technology to prevent and treat sexually transmitted infections (STIs). Moreover, many EF technologies focus on encapsulating the active agent, relative to utilizing the surface to impart biofunctionality. Here we describe a method to fabricate and surface-modify poly(lactic-co-glycolic) acid (PLGA) electrospun fibers, with the potent antiviral lectin Griffithsin (GRFT). PLGA is an FDA-approved polymer that has been widely used in drug delivery due to its outstanding chemical and biocompatible properties. GRFT is a natural, potent, and safe lectin that possesses broad activity against numerous viruses including human immunodeficiency virus type 1 (HIV-1). When combined, GRFT-modified fibers have demonstrated potent inactivation of HIV-1 in vitro. This manuscript describes the methods to fabricate and characterize GRFT-modified EFs. First, PLGA is electrospun to create a fiber scaffold. Fibers are subsequently surface-modified with GRFT using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS)chemistry. Scanning electron microscopy (SEM) was used to assess the size and morphology of surface-modified formulations. Additionally, a gp120 or hemagglutinin (HA)-based ELISA may be used to quantify the amount of GRFT conjugated to, as well as GRFT desorption from the fiber surface. This protocol can be more widely applied to fabricate fibers that are surface-modified with a variety of different proteins.

This manuscript describes the procedure to fabricate and characterize Griffithsin-modified poly(lactic-co-glycolic acid) electrospun fibers that demonstrate potent adhesive and antiviral activity against human immunodeficiency virus type 1 infection in vitro. Methods used to synthesize, surface-modify, and characterize the resulting morphology, conjugation, and desorption of Griffithsin from surface-modified fibers are described.

Griffithsin 修饰纤维支架预防性传播感染的制备与表征

Electrospun fibers (EFs) have been widely used in a variety of therapeutic applications; however, they have only recently been applied as a technology to ...

Large-area Scanning Probe Nanolithography Facilitated by Automated Alignment and Its Application to Substrate Fabrication for Cell Culture Studies

Scanning probe microscopy has enabled the creation of a variety of methods for the constructive (&#39;additive&#39;) top-down fabrication of nanometer-scale features. Historically, a major drawback of scanning probe lithography has been the intrinsically low throughput of single probe systems. This has been tackled by the use of arrays of multiple probes to enable increased nanolithography throughput. In order to implement such parallelized nanolithography, the accurate alignment of probe arrays with the substrate surface is vital, so that all probes make contact with the surface simultaneously when lithographic patterning begins. This protocol describes the utilization of polymer pen lithography to produce nanometer-scale features over centimeter-sized areas, facilitated by the use of an algorithm for the rapid, accurate, and automated alignment of probe arrays. Here, nanolithography of thiols on gold substrates demonstrates the generation of features with high uniformity. These patterns are then functionalized with fibronectin for use in the context of surface-directed cell morphology studies.

Here we present a protocol for wide-area scanning probe nanolithography enabled by the iterative alignment of probe arrays, as well as the utilization of lithographic patterns for cell-surface interaction studies.

基于自动对准的大面积扫描探针光刻及其在细胞培养研究中的应用

Scanning probe microscopy has enabled the creation of a variety of methods for the constructive (&#39;additive&#39;) top-down fabrication of ...

Fabrication and Characterization of Optical Tissue Phantoms Containing Macrostructure

The rapid development of new optical imaging techniques is dependent on the availability of low-cost, customizable, and easily reproducible standards. By replicating the imaging environment, costly animal experiments to validate a technique may be circumvented. Predicting and optimizing the performance of in vivo and ex vivo imaging techniques requires testing on samples that are optically similar to tissues of interest. Tissue-mimicking optical phantoms provide a standard for evaluation, characterization, or calibration of an optical system. Homogenous polymer optical tissue phantoms are widely used to mimic the optical properties of a specific tissue type within a narrow spectral range. Layered tissues, such as the epidermis and dermis, can be mimicked by simply stacking these homogenous slab phantoms. However, many in vivo imaging techniques are applied to more spatially complex tissue where three dimensional structures, such as blood vessels, airways, or tissue defects, can affect the performance of the imaging system. 
This protocol describes the fabrication of a tissue-mimicking phantom that incorporates three-dimensional structural complexity using material with optical properties of tissue. Look-up tables provide India ink and titanium dioxide recipes for optical absorption and scattering targets. Methods to characterize and tune the material optical properties are described. The phantom fabrication detailed in this article has an internal branching mock airway void; however, the technique can be broadly applied to other tissue or organ structures.

Optical tissue phantoms are essential tools for calibration and characterization of optical imaging systems and validation of theoretical models. This article details a method for phantom fabrication that includes replication of tissue optical properties and three-dimensional tissue structure.

含有宏观结构的光学组织幻影的制备与表征

The rapid development of new optical imaging techniques is dependent on the availability of low-cost, customizable, and easily reproducible standards. By ...

Detection of Endotoxin in Nano-formulations Using Limulus Amoebocyte Lysate (LAL) Assays

When present in pharmaceutical products, a Gram-negative bacterial cell wall component endotoxin (often also called lipopolysaccharide) can cause inflammation, fever, hypo- or hypertension, and, in extreme cases, can lead to tissue and organ damage that may become fatal. The amounts of endotoxin in pharmaceutical products, therefore, are strictly regulated. Among the methods available for endotoxin detection and quantification, the Limulus Amoebocyte Lysate (LAL) assay is commonly used worldwide. While any pharmaceutical product can interfere with the LAL assay, nano-formulations represent a particular challenge due to their complexity. The purpose of this paper is to provide a practical guide to researchers inexperienced in estimating endotoxins in engineered nanomaterials and nanoparticle-formulated drugs. Herein, practical recommendations for performing three LAL formats including turbidity, chromogenic and gel-clot assays are discussed. These assays can be used to determine endotoxin contamination in nanotechnology-based drug products, vaccines, and adjuvants.

Detection of Endotoxin in Nano-formulations Using Limulus Amoebocyte Lysate LAL Assays

Detection of endotoxins in engineered nanomaterials represents one of the grand challenges in the field of nanomedicine. Here, we present a case study that describes the framework composed of three different LAL formats to estimate potential endotoxin contamination in nanoparticles.

用利穆鲁布莱巴细胞裂解液 (lal) 法检测纳米配方中的内毒素

When present in pharmaceutical products, a Gram-negative bacterial cell wall component endotoxin (often also called lipopolysaccharide) can cause ...

Focused Ion Beam Lithography to Etch Nano-architectures into Microelectrodes

With advances in electronics and fabrication technology, intracortical microelectrodes have undergone substantial improvements enabling the production of sophisticated microelectrodes with greater resolution and expanded capabilities. The progress in fabrication technology has supported the development of biomimetic electrodes, which aim to seamlessly integrate into the brain parenchyma, reduce the neuroinflammatory response observed after electrode insertion and improve the quality and longevity of electrophysiological recordings. Here we describe a protocol to employ a biomimetic approach recently classified as nano-architecture. The use of focused ion beam lithography (FIB) was utilized in this protocol to etch specific nano-architecture features into the surface of non-functional and functional single shank intracortical microelectrodes. Etching nano-architectures into the electrode surface indicated possible improvements of biocompatibility and functionality of the implanted device. One of the benefits of using FIB is the ability to etch on manufactured devices, as opposed to during the fabrication of the device, facilitating boundless possibilities to modify numerous medical devices post-manufacturing. The protocol presented herein can be optimized for various material types, nano-architecture features, and types of devices. Augmenting the surface of implanted medical devices can improve the device performance and integration into the tissue.

We have shown that the etching of nano-architecture into intracortical microelectrode devices may reduce the inflammatory response and has the potential to improve electrophysiological recordings. The methods described herein outline an approach to etch nano-architectures into the surface of non-functional and functional single shank silicon intracortical microelectrodes.

聚焦 Ion 光束平版印刷到蚀刻纳米架构到微电极

With advances in electronics and fabrication technology, intracortical microelectrodes have undergone substantial improvements enabling the production of ...