我们感谢在康奈尔大学教授保罗·麦克尤恩早期讨论。这项工作是支持的启动基金提供的密歇根大学和美国国家科学基金会可扩展的纳米制造计划（DMR-1120187）。这项工作在美国密歇根大学，由美国国家科学基金会资助的美国国家纳米技术基础设施网络的成员劳瑞加工设施。

1。单壁碳纳米管生长催化剂图案<ol><li>首先，用低压化学气相沉积（CVD）生长为500nm的Si 3 N 4 / 500nm的SiO 2膜的顶部的硅晶片。 </li><li>旋涂一层光致抗蚀剂（PR），以500rpm，持续5秒，然后4,000 rpm离心40秒。 </li><li>晶片在115℃下烘烤90秒。 </li><li>与催化剂（ 图1）的矩形的凹坑中使用的光掩模和晶片暴露在UV（365 nm）的辐照度为300毫焦耳/厘米2，持续0.3秒。曝光后晶片在115℃下烘烤90秒。 </li></ol> 提示:5微米×5微米，10微米×5微米等设计不同大小的坑， 如考虑到单壁碳纳米管的化学气相沉积（CVD）的生长过程中变异。 <ol start="5"><li>开发晶片开发商70秒轻轻晃动晶片经由过程。 </li><li> DI年末冲洗晶圆r为2分钟，然后用氮气（N 2）枪吹干。 </li><li>开发晶片加载到电子束蒸发器腔和存款0.5 nm的铁（Fe）的上面的腔室的压力为10 -6托。 </li><li>切块的晶圆切割成较小的模具1.5厘米×1.5厘米。 </li><li>将光致抗蚀剂通过浸渍在温水中丙酮和异丙醇（IPA），每次10分钟。这留下铁催化剂纳米管的生长的长方形坑。 </li></ol> 2。 CVD生长碳纳米管<ol><li>将催化剂涂覆的模具的CVD生长炉中的石英管。 </li></ol> 提示:确定纳米管的生长的甜蜜点。增长是均匀的面积为2英寸x 2英寸下游炉（ 图2c）。 <ol start="2"><li>基板在空气中在880℃下退火一小时，以除去光致抗蚀剂残余物（ 图2a）。允许降温。 </li><li>用Ar吹扫室坤3的SLM（标准升每分钟）的5分钟。 </li><li>斜坡上升至800℃的炉中，在管的中心，同时保持1 SLM的氩气（ 图2b）的流动。 </li><li>流0.2 SLM的氢气为5分钟，以减少的催化剂粒子， 即，将铁的氧化物铁。 </li><li>介绍5.5的SCCM（标准立方厘米每分钟），乙烯（C 2 H 4）35分钟增长碳纳米管。保持H 2流量0.2 SLM整个过程。从这个配方获得单壁碳纳米管的长度是20微米（微米）。 </li><li>允许炉冷却至室温下，用一个小的氩气流量。 </li></ol> 3。单壁碳纳米管场效应晶体管制造<ol><li>设计的光掩模（ 图1）定义的源极-漏极电极的电流-电压（IV）特性的碳纳米管。 </li></ol> 提示:延长电极接触垫远APAR吨模具，使他们仍然可以访问后甚至放下一个微流体邮票上的活跃碳纳米管区域。 <ol start="2"><li>按照步骤1.2 -1.6定义接触面积金属沉积。 </li><li>存款的Ti /金0.5 nm/50的纳米电子束蒸发室在10 -6托的源漏接触。 </li><li>让丙酮过夜金属升空的模具。升空后，浸在IPA模具10分钟，然后吹干，用N 2枪。 </li><li>不要毯子为500nm的电子束蒸发沉积SiO 2的栅极电介质，在10 -6托。 </li><li>设计的光掩模（ 图1）限定的栅极电极。 </li><li>按照步骤1.2-1.6定义区域栅极金属沉积。 </li><li>蒸发50 nm/50的Cr / Au纳米电子束蒸发器的顶部栅电极。按照步骤3.4金属升空。 </li></ol> 提示:使用粗壮的镀铬层，以增加强度Øf暂停顶栅。门的尺寸也悬挂成功的关键。 <ol start="9"><li>毯上沉积一层薄的SiO 2（20纳米）的顶部电极钝化。 </li><li>光罩设计（ 图1），打开一个战壕在SiO 2，访问碳纳米管通道。焊垫设计在相同的掩模蚀刻区域打开远离单壁碳纳米管的通道访问源，漏和栅电极的区域。 </li><li>按照步骤1.2-1.6图案公关开辟沟渠湿蚀刻的SiO 2。 </li><li>湿法腐蚀的蒸发SiO 2的使用1:20的BHF溶液在3分钟和30秒。的Si 3 N 4提供了一个蚀刻停止层，以防止进一步渗透的BHF。 </li></ol> 提示:建议蚀刻时间校准。 <ol start="13"><li>在去离子水中彻底冲洗装置，然后在IPA中浸入5分钟。使用N 2枪吹干。该设备STructure由于粗壮的镀铬层保持完好。 </li></ol> 4。化学修饰碳纳米管侧壁<ol><li>准备6毫1 pyrenebutanoic的酸琥珀酰亚胺酯（PBSE）在二甲基甲酰胺（DMF）中的溶液中。 </li><li>孵育单壁碳纳米管FET在这个链接的分子溶液在室温下1小时死亡。 </li><li>彻底清洗模具，在DMF洗去过量的试剂。吹干设备。 </li><li>准备一个20mg/ml的溶液中生物素-3，6 - （生物素PEO胺-BPA）在去离子水中的生物素化的单壁碳纳米管dioxaoctanediamine。 </li><li>电路小片在该溶液中孵育18小时后，模具在去离子水中彻底冲洗并吹干。重视BPA的PBSE连接分子。 </li><li>准备1mg/ml的链霉亲和素溶液pH值在7.2 PBS溶液链霉亲和素结合。 </li><li>对于静态测量，模具在链霉抗生物素蛋白溶液中孵育20分钟，完全官能化的生物素化的单壁碳纳米管。索罗ughly冲洗并吹干模具。实时检测，杜绝PDMS流道（步骤6）然后流的链霉亲和素溶液中离子强度高的背景链霉亲和素结合（ 图3）。 </li></ol> 注:我们冲洗模具，在模具使用挤压瓶胶DI水（50毫升）。然后，我们的电路小片移动到另一培养皿中含有去离子水，1分钟左右，电路小片移动。我们重复这两个步骤总的8-10倍。 5。制备的聚二甲基硅氧烷（PDMS）流体腔模具<ol><li>在一个称量杯，倒入9份（重量）的PDMS单体，并添加1份（重量）的固化剂，充分混合两个。 </li><li>脱气的混合物25分钟，在干燥器中。气泡会通过混合物上升而离开。 </li></ol> 提示:如果混合物开始发泡，发泄室，让它沉淀下来的几个秒钟，然后再次脱气。 <ol start="3"><li>在培养皿中放置一个新的硅片。脱气后的PDMS混合物倒入在它的上面有一个PDMS层晶片上方5mm。 </li><li>陪替氏培养皿在70℃的烘箱中放置1小时。 </li><li>取出培养皿中，让它冷却下来。使用手术刀切出一块长方形的PDMS，将其拉出使用镊子。 </li></ol> 提示:PDMS侧直接与硅片接触 ​​是干净的，非常平坦。此方将单壁碳纳米管场效应管模具接触。要小心，不要污染。 <ol start="6"><li>上下颠倒放置的矩形模具，并在使用活检冲床（3毫米直径）从平到另一侧钻了一个洞。这将确保没有粗糙的边缘上侧扁PDMS（ 图4a）。 </li><li>的PDMS室放置在设备顶部的仔细对齐，它的有源区上方的所制作的单壁碳纳米管场效应管模具（&lt;强大的图4a，b）条。轻轻点击它，以确保模具邮票。侧扁债券到模具，，提供防漏室。 </li></ol> 提示:这可以通过用裸眼或用光学显微镜有足够的工作空间。 PDMS如果不沾（一般如果电路小片和/或PDMS印章不干净的），氧等离子体（20瓦，15秒），以协助对PDMS粘接。使用血浆权力高于这会导致更强的粘接，但是，我们已经看到翻录电极，而在这种情况下删除的PDMS。 <ol start="8"><li>取出后PDMS印章电气测试和之前下化学官能一步的模具浸入去离子水，轻轻抬起邮票。 </li></ol> 6。制备微流通道<ol><li>取一干净的硅晶片，并将其放置在电热板上，在200℃下进行5分钟以除去任何湿气。 </li><li>旋涂SU-8 2015 500转（100转/秒斜坡率），持续5秒，然后1,250 rpm离心30秒，在300转/秒的斜坡率。这给出了30μm厚的SU-8层上的硅晶片。 </li><li>软烤晶圆在95℃下5分钟。 </li><li>设计的光掩模（ 图4c）定义的300μm宽的流路图案的单壁碳纳米管的面积之上。 </li></ol> 提示:为避免结构倒塌的通道宽度:，足够高度比为10:1（300微米:在这种情况下，30微米）。 <ol start="5"><li>使用365纳米的紫外线光刻法定义的流路，用紫外曝光时间为0.9秒。 </li><li>烘烤后的电路小片在95℃下5分钟。 </li><li>发展伴随着轻轻摇动5分钟的SU-8开发的模式。 </li><li>冲洗晶圆IPA和N 2枪吹干。 </li><li>按照步骤5.1-5.2准备PDMS混合物。 </li><li>随着硅烷化剂TRIC 2-3下拉晶片放置在干燥器中的SU-8的模具hloro（3，3，3 - 三氟丙基）硅烷在培养皿中。打开真空泵在真空中1小时让晶片坐。 </li><li>脱气后的PDMS混合物倒入到晶片上，并在70℃的烘箱中加热1小时。 </li><li>切PDMS模具（SU-8负）使用手术刀。 </li><li>将PDMS印章倒过来，用活检冲头（0.75毫米直径）钻一个孔，在每一端的流道。确保从平面侧（一侧与硅片接触 ​​）到其他钻孔，以避免粗糙的边缘（ 图4e）。 </li><li> PDMS流室放置在设备顶部的仔细对准顶部制作的单壁碳纳米管的场效应管的模具，在显微镜下的有源区上。轻轻点击它，以确保模具邮票。侧扁债券到模具，，提供防漏室。 （ 图4c和4d） </li><li>推入聚乙烯管插入孔中并将 ​​另一端连接到流体的源极和漏极注射器（FIGURE 4E）。 </li><li>将注射器的注射泵系统，以保持控制，通过该信道（ 图6）的流体流动。 </li></ol> 7。直流电气测量设置的<ol><li>连接电压数据采集卡的端口的单壁碳纳米管场效应管的源极和栅极接触。 </li><li>通过电流的前置放大器，数据采集卡输入端口连接漏极接触。 </li><li>应用30毫伏（MV）源接触，扫的栅极电压，并记录电流漏（ 图5a）。 </li></ol> 提示:测量溶液中，保持栅极电压扫描参数| 0.7伏以内，以避免漏电和金属栅电极和解决方案之间的反应。 8。 AC电气测量设置<ol><li>来自锁相放大器的外部调制信号的端口上的频率发生器，用于设置连接的Ref信号AM调制freque的NCY输出。 </li><li>连接的单壁碳纳米管的场效应管的源极接触的频率发生器和直流电压从数据采集卡的使用偏置T形（ 图5b和5c）的AM调制的RF输出端口。 </li><li>将门接触电压端口的数据采集卡。 </li><li>漏极接触连接到锁相放大器读交流电流通过碳纳米管。通过数据采集输入端口读取的电流的幅度和相位。 </li><li>源的直流电压保持在0伏和AM信号的频率在200千赫（kHz）。 </li><li>扫栅极电压和测量的漏电流。 </li><li>我在不同的频率组合V G扫描频率增加，并重复步骤8.6。 </li></ol> 9。电气测量解决方案（无流量） <ol><li>准备:1 mM氯化钠，氯化钠10毫米和100毫米氯化钠盐溶液从5M的NaCl原液。 </li><li>以SWNT设备从步骤3.13。步骤4.1-4.5获得biotinylate的开展D设备。 </li><li>按照步骤5把PDMS室，设备顶部的。 </li><li>填充室DI水用吸管。 </li><li>按照步骤8混频测量不同频率。 </li><li>重复9.4三种不同的盐溶液，10 mM氯化钠，氯化钠100毫米1毫米氯化钠。 </li></ol> 提示:使用吸管撤回先前的解决方案，然后冲洗室多次与新的解决方案。随时切换，从低到高浓度的解决方案。 <ol start="7"><li>将PDMS印章用镊子轻轻提起邮票。 </li><li>用去离子水彻底冲洗设备。 </li><li>开展链霉亲和素结合在4.6-4.7解释。 </li><li>重复步骤9.3-9.6。 </li></ol> 10。电气测量解决方案（实时流） <ol><li>准备100 mM氯化钠盐溶液从5 M氯化钠股票解决方案开始。 </li><li>单壁碳纳米管的设备从STEp 3.13。开展步骤4.1-4.5获得生物素标记的设备。 </li><li>将以下的步骤（6）的移动设备上的微流体流动通道中..撤回模式操作的微流体通道的一端连接一个空的注射器。在其另一端连接注射器100mM NaCl的溶液中与背景。 </li><li>电气测量的详细步骤8。固定的频率（F = 10兆赫）和栅极偏置电压（V = 0）。 </li><li>开始注射泵在停药模式（流速= 0.4毫升-1小时），并监测随时间的电流信号。在100mM NaCl的链霉抗生物素蛋白-生物素的结合（ 图6）和监控信号的变化，开关1mg/ml的链霉抗生物素蛋白的溶液。 </li></ol>

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A., Dekker, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enzyme-coated+carbon+nanotubes+as+single-molecule+biosensors.">Enzyme-coated carbon nanotubes as single-molecule biosensors.</a> Nano Letters. 3, 727-730 (2003).</li><li>Snow, E. S., Perkins, F. K., Houser, E. J., Badescu, S. C., Reinecke, T. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemical+detection+with+a+single-walled+carbon+nanotube+capacitor.">Chemical detection with a single-walled carbon nanotube capacitor.</a> Science. 307, 1942-1945 (2005).</li><li>Kong, J., Franklin, N. 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=Nanotube+molecular+wires+as+chemical+sensors.">Nanotube molecular wires as chemical sensors.</a> Science. 287, 622-625 (2000).</li><li>Star, A., Tu, E., 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=Label-free+detection+of+DNA+hybridization+using+carbon+nanotube+network+field-effect+transistors.">Label-free detection of DNA hybridization using carbon nanotube network field-effect transistors.</a> Proceedings of the National Academy of Sciences of the United States of America. 103, 921-926 (2006).</li><li>Patolsky, F., Zheng, G. F., Lieber, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanowire-based+biosensors.">Nanowire-based biosensors.</a> Analytical Chemistry. 78, 4260-4269 (2006).</li><li>Stern, E., Klemic, J. F., 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=Label-free+immunodetection+with+CMOS-compatible+semiconducting+nanowires.">Label-free immunodetection with CMOS-compatible semiconducting nanowires.</a> Nature. 445, 519-522 (2007).</li><li>Krivitsky, V., Hsiung, L. -. 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=Nanowires+Forest-Based+On-Chip+Biomolecular+Filtering,+Separation+and+Preconcentration+Devices:+Nanowires+Do+it+All.">Nanowires Forest-Based On-Chip Biomolecular Filtering, Separation and Preconcentration Devices: Nanowires Do it All.</a> Nano Letters. 12, 4748-4756 (2012).</li><li>Kong, J., Soh, H. T., Cassell, A. M., Quate, C. F., Dai, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+individual+single-walled+carbon+nanotubes+on+patterned+silicon+wafers.">Synthesis of individual single-walled carbon nanotubes on patterned silicon wafers.</a> Nature. 395, 878-881 (1998).</li><li>Liu, G., Velasco, J., Bao, W. Z., Lau, C. N. <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+graphene+p-n-p+junctions+with+contactless+top+gates.">Fabrication of graphene p-n-p junctions with contactless top gates.</a> Applied Physics Letters. 92, (2008).</li><li>Katz, E., Willner, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Probing+biomolecular+interactions+at+conductive+and+semiconductive+surfaces+by+impedance+spectroscopy:+Routes+to+impedimetric+immunosensors,+DNA-Sensors,+and+enzyme+biosensors.">Probing biomolecular interactions at conductive and semiconductive surfaces by impedance spectroscopy: Routes to impedimetric immunosensors, DNA-Sensors, and enzyme biosensors.</a> Electroanalysis. 15, 913-947 (2003).</li><li>K'Owino, I. O., Sadik, O. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impedance+spectroscopy:+A+powerful+tool+for+rapid+biomolecular+screening+and+cell+culture+monitoring.">Impedance spectroscopy: A powerful tool for rapid biomolecular screening and cell culture monitoring.</a> Electroanalysis. 17, 2101-2113 (2005).</li><li>Elnathan, R., Kwiat, 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=Biorecognition+Layer+Engineering:+Overcoming+Screening+Limitations+of+Nanowire-Based+FET+Devices.">Biorecognition Layer Engineering: Overcoming Screening Limitations of Nanowire-Based FET Devices.</a> Nano Letters. 12, 5245-5254 (2012).</li></ol>

作者宣称，他们有没有竞争经济利益。

碳纳米管的生长，不仅取决于炉况，但也基板清洁度。必须仔细校准，一旦固定，它们都或多或少的稳定的最佳气体流速，温度和压力的增长。即使这些条件得到满足，我们发现增长取决于图案的催化剂，面积，金额的催化剂和基板清洁度。因此，我们注册成立了多个催化剂坑的大小占增长的变异。一小时的高温退火步骤有助于从基片上除去任何污染物，例如:PR残余物等， 图2示出的...

当一个带电的分子结合到一个单壁碳纳米管或NW电子传感器，它可以捐赠/接受电子或作为本地静电门。在这两种情况下，可以改变结合的分子的电荷密度，在单壁碳纳米管或洒水通道，导致的传感器测得的直流电导的变化。 15-20分子种类繁多的已成功检测研究纳米传感器的直流特性，在这样的结合事件。即使负责检测的传感机理有很多优势，包括无标记检测21毫微摩尔灵敏度22，和电子读出能力15，它是有效的，只有在低离子强度的解决方案。在高离子强度的解决方案，直流检测离子筛选6-8阻碍。甲充电表面吸引，形成表面附近的双电层（EDL）从该溶液中的反离子。 EDL有效地筛选这些费用。作为T他的离子强度的溶液的增加，EDL的变窄和筛选的增加。该屏蔽效应的Debye屏蔽长度λD，其特征在于<img alt="公式1" fo:src="/files/ftp_upload/50438/50438eq1highres.jpg" src="/files/ftp_upload/50438/50438eq1.jpg" /> 式中，ε是介质的介电常数，K B为玻尔兹曼常数，T是温度，q是电子电荷，c为电解质溶液的离子强度。对于一个典型的100mM的缓冲溶液中，λD是约1纳米的表面电势在几个纳米的距离完全筛选。其结果是，大多数基于单壁碳纳米管或纳米线的纳米电子传感器操作无论是在干燥状态下20或低离子强度的解决方案5,15,17,21-22（C〜1纳米- 10毫摩尔），其他样品需要进行脱盐步骤15,23。点医疗诊断设备需要在生理离子强度，来样加工能力有限的病人站点。因此，减轻离子筛查效果是POC纳米电子生物传感器的开发和实施的关键。 我们减轻离子屏蔽效应，基于单壁碳纳米管的纳米电子传感器在兆赫频率范围经营。该协议提供了在这里制造的单壁碳纳米管晶体管为基础的纳米电子传感平台和高频混合测量生物分子检测。单壁碳纳米管生长的化学气相沉积图案与Fe催化剂24的基板上。对于我们的单壁碳纳米管晶体管，我们将暂停顶栅25以上500纳米的碳纳米管，这有助于提高高频传感器响应，也可以让一个紧凑的MICR邻流体腔密封装置。单壁碳纳米管晶体管的运行为高频率混频器9-11为了克服背景离子屏蔽效应。在高频时，溶液中的离子移动，没有足够的时间来形成的EDL和生物分子偶极子波动仍然可以门的单壁碳纳米管生成一个混合的电流，这是我们的传感信号。混频的产生是由于碳纳米管FET的非线性伏安特性 。我们的检测技术不同于常规技术充电检测和阻抗谱26-27。首先，我们检测生物分子的偶极子的相关费用，而不是在高频率。其次，高跨导的单壁碳纳米管的晶体管提供了一个内部​​的感测信号的增益。这省却了在高频阻抗测量的情况下，无需进行外部放大。最近，其他团体也高BA解决生物分子检测的ckground浓度23,28。然而，这些方法更复杂，需要复杂的制造或受体分子化学工程小心。我们的高频率的单壁碳纳米管传感器采用一个简单的设计，并采用混合属性的碳纳米管晶体管的固有频率。我们有能力，以减轻离子屏蔽效应，因此看好一个新的生物传感平台进行实时的护理点检测，需要直接在生理条件下运作的生物传感器。

<table><tbody><tr><td colspan="4">&lt;strong&gt;REAGENTS&lt;/strong&gt;</td></tr><tr><td colspan="4">Reagents which were provided within Lurie Nanofabrication Facility (University of Michigan) are marked as LNF in the catalogue column. Chemicals which require protective equipment (gloves, safety goggles, face mask, apron) and/or fume hood are denoted with PPE in comments section.</td></tr><tr><td>Silicon wafers (P-type, &amp;lt;100&amp;gt;, 500-550 &amp;mu;m thick)</td><td>Silicon Valley Microelectronics</td><td></td><td></td></tr><tr><td>SPR 220 3.0</td><td>Dow (Rohm and Haas)</td><td>Megaposit SPR</td><td>PPE</td></tr><tr><td>AZ 300MIF</td><td>AZ Electronic Material Corporation</td><td></td><td>PPE</td></tr><tr><td>Acetone</td><td>J T Baker</td><td>9005-05</td><td>PPE</td></tr><tr><td>Isopropanol (IPA)</td><td>J T Baker</td><td>9079-05</td><td></td></tr><tr><td>Buffered Hydrofluoric Acid</td><td>Transene</td><td></td><td>PPE</td></tr><tr><td>1-Pyrene Butanoic Acid, succinimidyl ester</td><td>Molecular Probes</td><td>P130</td><td>PPE</td></tr><tr><td>Biotin PEO Amine</td><td>Thermo Scientific</td><td>EZ- Link PEG2 Biotin, # 21346</td><td>PPE</td></tr><tr><td>Streptavidin</td><td>Invitrogen</td><td>S 888</td><td>PPE</td></tr><tr><td>Dimethylformamide</td><td>MP Biomedicals</td><td>0219514791</td><td>PPE</td></tr><tr><td>Polydimethylsiloxane Elastomer Base and Curing Agent</td><td>Dow Corning</td><td>Sylgard 184 Elastomer Kit</td><td>PPE</td></tr><tr><td>SU-8 2015</td><td>Microchem</td><td>Y111064</td><td>PPE</td></tr><tr><td>SU-8 Developer</td><td>Microchem</td><td>Y020100</td><td>PPE</td></tr><tr><td>Silanizing agent</td><td>Sigma Aldrich</td><td>452807</td><td>PPE</td></tr><tr><td>Hydrogen</td><td>Purity Plus</td><td>LNF</td><td></td></tr><tr><td>Ethylene</td><td>Purity Plus</td><td>LNF</td><td></td></tr><tr><td>Argon</td><td>Purity Plus</td><td>LNF</td><td></td></tr><tr><td>Phosphate Buffer Saline System</td><td>Sigma Aldrich</td><td>PBS1</td><td></td></tr><tr><td colspan="4">&lt;strong&gt;EQUIPMENT&lt;/strong&gt;</td></tr><tr><td colspan="4">Equipment provided by Lurie Nanofabrication Facility (University of Michigan) is denoted as LNF in Catalogue column.</td></tr><tr><td>GCA 200 Autostepper</td><td>GCA</td><td>LNF</td><td></td></tr><tr><td>Low Pressure Chemical Vapor Deposition Tool</td><td>Tempress</td><td>LNF</td><td></td></tr><tr><td>e-beam Evaporator</td><td>Enerjet</td><td>LNF</td><td></td></tr><tr><td>CNT growth Furnace</td><td>First Nano</td><td>Easy Tube 3000 (LNF)</td><td></td></tr><tr><td>Photomasks</td><td>Nanofilm</td><td>LNF</td><td></td></tr><tr><td>Petri dish (150mm)</td><td></td><td>LNF</td><td></td></tr><tr><td>Desiccator</td><td>Bel-Art</td><td>F420100000</td><td></td></tr><tr><td>Biopsy Punch</td><td>Ted Pella</td><td>15071/78</td><td></td></tr><tr><td>Scalpel</td><td>Ted Pella</td><td>548</td><td></td></tr><tr><td>Polyethylene Tubing PE-50</td><td>VWR</td><td>20903-414</td><td></td></tr><tr><td>Syringe Pump</td><td>New Era Pump Systems</td><td>NE-1000</td><td></td></tr><tr><td>Syringe</td><td>Fisher Scientific</td><td>BD Safety-Lok Syringes</td><td></td></tr><tr><td>Syringe Needles</td><td>Fisher Scientific</td><td>14-821-13A</td><td></td></tr><tr><td>DAQ card</td><td>National Instruments</td><td>779111-01</td><td></td></tr><tr><td>GPIB connector</td><td>National Instruments</td><td>778032-51</td><td></td></tr><tr><td>Lock-in Amplifier</td><td>Stanford Research Systems</td><td>SR 830</td><td></td></tr><tr><td>Frequency Generator</td><td>HP Agilent</td><td>8648B, 9kHz -2GHz</td><td></td></tr><tr><td>Bias Tee</td><td>Picosecond</td><td>5575A-104</td><td></td></tr><tr><td>Current Preamplifier</td><td>DL Instruments, LLC</td><td>DL 1211</td><td></td></tr><tr><td>BNC cables</td><td>Allied Electronics</td><td>665-xxxx</td><td></td></tr><tr><td>SMA cables</td><td>Sentro Tech Corp</td><td>SCF65141</td><td></td></tr></tbody></table>

fabrication of carbon nanotube high-frequency nanoelectronic biosensor for sensing in high ionic strength solutions

独特的电子性质和高表面体积比单壁碳纳米管（SWNT）和半导体纳米线（NW）1-4让他们很好的候选人高灵敏度生物传感器。当一个带电的分子结合到这样的传感器表面，改变载流子浓度5中的传感器，其直流电导的变化。然而，在离子溶液中的带电表面也吸引从该溶液中的反离子，形成双电层（EDL）。此EDL有效屏幕关闭充电，在生理条件下〜100毫摩尔（MM），特性电荷屏蔽长度（德拜长度）小于一个纳米（nm）。因此，在高离子强度的解决方案，充电（DC）的检测是从根本上阻碍了6-8。 我们克服电荷屏蔽效应通过检测分子偶极子，而不是在高频收费，经营碳nanot的UBE场效应晶体管高频混频器9-11。在高频时，的AC驱动力可以不再克服溶液阻力和溶液中的离子，没有足够的时间形成的EDL。另外，混频技术使我们能够工作在频率足够高，以克服离子筛选，而检测到的感测信号在较低频率的11-12。此外，单壁碳纳米管的晶体管的高跨导，提供了一个内部​​的感测信号，避免了需要外部信号放大器的增益。 在这里，我们描述协议（一）制备单壁碳纳米管晶体管，（二）生物分子功能化碳纳米管13，（C）到设备设计和邮票聚二甲基硅氧烷（PDMS）微流控室14，（D）进行高频感应离子强度不同的解决方案11。

与一个暂停的顶栅晶体管的单壁碳纳米管的扫描电子显微镜图像如图7a所示。悬架25的栅极的尺寸是至关重要的。目前的设计尺寸（长x宽x厚= 25微米×1微米×100纳米）。栅电极由50纳米Cr/50纳米金，粗壮的镀铬层悬挂结构增加了更多的力量。也证实了顶部栅极和漏极（ 图7b）之间的泄漏电流的情况下的悬浮结构。 我们用生物素 - 链霉亲和素配体 ...

Watch this Scientific Journal Video about Fabrication of Carbon Nanotube High-Frequency Nanoelectronic Biosensor for Sensing in High Ionic Strength Solutions at JoVE.com

Fabrication of Carbon Nanotube High-Frequency Nanoelectronic Biosensor for Sensing in High Ionic Strength Solutions

我们描述了基于碳纳米管的高频生物传感器的设备制造和测量协议。高频感应技术减轻了根本的离子（德拜）的屏蔽效应，并允许碳纳米管传感器工作在高离子强度的解决方案，在传统的电子生物传感器失败。我们的技术提供了一个独特的平台，为护理点（POC）在生理条件下运行的电子生物传感器。

制备碳纳米管高频纳电子生物传感器的传感高离子强度的解决方案

The unique electronic properties and high surface-to-volume ratios of single-walled carbon nanotubes (SWNT) and semiconductor nanowires (NW) 1-4 make them ...

fabrication-carbon-nanotube-high-frequency-nanoelectronic-biosensor

Universidad de Cartagena UDEC

Research

JoVE Journal

Bioengineering

18.1K 次观看.  University of Michigan - Ann Arbor. 我们描述了基于碳纳米管的高频生物传感器的设备制造和测量协议。高频感应技术减轻了根本的离子（德拜）的屏蔽效应，并允许碳纳米管传感器工作在高离子强度的解决方案，在传统的电子生物传感器失败。我们的技术提供了一个独特的平台，为护理点（POC）在生理条件下运行的电子生物传感器。

视频: Fabrication of Carbon Nanotube High-Frequency Nanoelectronic Biosensor for Sensing in High Ionic Strength Solutions

Fluorescent Nanoparticles for the Measurement of Ion Concentration in Biological Systems

Tightly regulated ion homeostasis throughout the body is necessary for the prevention of such debilitating states as dehydration.1 In contrast, rapid ion fluxes at the cellular level are required for initiating action potentials in excitable cells.2 Sodium regulation plays an important role in both of these cases; however, no method currently exists for continuously monitoring sodium levels in vivo 3 and intracellular sodium probes 4 do not provide similar detailed results as calcium probes. In an effort to fill both of these voids, fluorescent nanosensors have been developed that can monitor sodium concentrations in vitro and in vivo.5,6 These sensors are based on ion-selective optode technology and consist of plasticized polymeric particles in which sodium specific recognition elements, pH-sensitive fluorophores, and additives are embedded.7-9 Mechanistically, the sodium recognition element extracts sodium into the sensor. 10 This extraction causes the pH-sensitive fluorophore to release a hydrogen ion to maintain charge neutrality within the sensor which causes a change in fluorescence. The sodium sensors are reversible and selective for sodium over potassium even at high intracellular concentrations.6 They are approximately 120 nm in diameter and are coated with polyethylene glycol to impart biocompatibility. Using microinjection techniques, the sensors can be delivered into the cytoplasm of cells where they have been shown to monitor the temporal and spatial sodium dynamics of beating cardiac myocytes.11 Additionally, they have also tracked real-time changes in sodium concentrations in vivo when injected subcutaneously into mice.3 Herein, we explain in detail and demonstrate the methodology for fabricating fluorescent sodium nanosensors and briefly demonstrate the biological applications our lab uses the nanosensors for: the microinjection of the sensors into cells; and the subcutaneous injection of the sensors into mice.

Fluorescent nanoparticles produced in our lab are used for imaging ion concentrations and ion fluxes in biological systems such as cells during signaling and interstitial fluid during physiological homeostasis.

在生物系统中的离子浓度测量荧光纳米粒子

Tightly regulated ion homeostasis throughout the body is necessary for the prevention of such debilitating states as dehydration.1 In contrast, rapid ion ...

科研

生物工程

Fabrication of Electrochemical-DNA Biosensors for the Reagentless Detection of Nucleic Acids, Proteins and Small Molecules

As medicine is currently practiced, doctors send specimens to a central laboratory for testing and thus must wait hours or days to 
receive the results. Many patients would be better served by rapid, bedside tests. To this end our laboratory and others have developed a versatile, reagentless 
biosensor platform that supports the quantitative, reagentless, electrochemical detection of nucleic acids (DNA, RNA), proteins (including antibodies) and small 
molecules analytes directly in unprocessed clinical and environmental samples. In this video, we demonstrate the preparation and use of several biosensors in this 
"E-DNA" class. In particular, we fabricate and demonstrate sensors for the detection of a target DNA sequence in a polymerase chain reaction mixture, an HIV-specific antibody and the drug cocaine. The preparation procedure requires only three hours of hands-on effort followed by an overnight incubation, and their use requires only minutes.

"E-DNA" sensors, reagentless, electrochemical biosensors that perform well even when challenged directly in blood and other complex matrices, have been adapted to the detection of a wide range of nucleic acid, protein and small molecule analytes. Here we present a general procedure for the fabrication and use of such sensors.

无试剂检测核酸，蛋白质和小分子的电化学DNA生物传感器的制备

As medicine is currently practiced, doctors send specimens to a central laboratory for testing and thus must wait hours or days to 
receive the results. ...

Fabrication of Low Temperature Carbon Nanotube Vertical Interconnects Compatible with Semiconductor Technology

We demonstrate a method for the low temperature growth (350 &#176;C) of vertically-aligned carbon nanotubes (CNT) bundles on electrically conductive thin-films. Due to the low growth temperature, the process allows integration with modern low-&#954; dielectrics and some flexible substrates. The process is compatible with standard semiconductor fabrication, and a method for the fabrication of electrical 4-point probe test structures for vertical interconnect test structures is presented. Using scanning electron microscopy the morphology of the CNT bundles is investigated, which demonstrates vertical alignment of the CNT and can be used to tune the CNT growth time. With Raman spectroscopy the crystallinity of the CNT is investigated. It was found that the CNT have many defects, due to the low growth temperature. The electrical current-voltage measurements of the test vertical interconnects displays a linear response, indicating good ohmic contact was achieved between the CNT bundle and the top and bottom metal electrodes. The obtained resistivities of the CNT bundle are among the average values in the literature, while a record-low CNT growth temperature was used.

A method for the growth of low temperature vertically-aligned carbon nanotubes, and the subsequent fabrication of vertical interconnect electrical test structures using semiconductor fabrication is presented.

低温碳纳米管垂直互连的制作兼容半导体技术

We demonstrate a method for the low temperature growth (350 &#176;C) of vertically-aligned carbon nanotubes (CNT) bundles on electrically conductive ...

工程学

Flow-assisted Dielectrophoresis: A Low Cost Method for the Fabrication of High Performance Solution-processable Nanowire Devices

Flow-assisted dielectrophoresis (DEP) is an efficient self-assembly method for the controllable and reproducible positioning, alignment, and selection of nanowires. DEP is used for nanowire analysis, characterization, and for solution-based fabrication of semiconducting devices. The method works by applying an alternating electric field between metallic electrodes. The nanowire formulation is then dropped onto the electrodes which are on an inclined surface to create a flow of the formulation using gravity. The nanowires then align along the gradient of the electric field and in the direction of the liquid flow. The frequency of the field can be adjusted to select nanowires with superior conductivity and lower trap density. 
In this work, flow-assisted DEP is used to create nanowire field effect transistors. Flow-assisted DEP has several advantages: it allows selection of nanowire electrical properties; control of nanowire length; placement of nanowires in specific areas; control of orientation of nanowires; and control of nanowire density in the device. 
The technique can be expanded to many other applications such as gas sensors and microwave switches. The technique is efficient, quick, reproducible, and it uses a minimal amount of dilute solution making it ideal for the testing of novel nanomaterials. Wafer scale assembly of nanowire devices can also be achieved using this technique, allowing large numbers of samples for testing and large-area electronic applications.

In this paper, flow assisted dielectrophoresis is demonstrated for the self-assembly of nanowire devices. The fabrication of a silicon nanowire field effect transistor is shown as an example.

流动辅助介: 一种低成本的制备高性能溶液可纳米线器件的方法

Flow-assisted dielectrophoresis (DEP) is an efficient self-assembly method for the controllable and reproducible positioning, alignment, and selection of ...

High Resolution Physical Characterization of Single Metallic Nanoparticles

Individual molecules can be detected and characterized by measuring the degree by which they reduce the ionic current flowing through a single nanometer-scale pore. The signal is characteristic of the molecule&#39;s physicochemical properties and its interactions with the pore. We demonstrate that the nanopore formed by the bacterial protein exotoxin Staphylococcus aureus alpha hemolysin (&#945;HL) can detect polyoxometalates (POMs, anionic metal oxygen clusters), at the single molecule limit. Moreover, multiple degradation products of 12-phosphotungstic acid POM (PTA, H3PW12O40) in solution are simultaneously measured. The single molecule sensitivity of the nanopore method allows for POMs to be characterized at significantly lower concentrations than required for nuclear magnetic resonance (NMR) spectroscopy. This technique could serve as a new tool for chemists to study the molecular properties of polyoxometalates or other metallic clusters, to better understand POM synthetic processes, and possibly improve their yield. Hypothetically, the location of a given atom, or the rotation of a fragment in the molecule, and the metal oxidation state could be investigated with this method. In addition, this new technique has the advantage of allowing the real-time monitoring of molecules in solution.&#160;

Here, we present a protocol to detect discrete metal oxygen clusters, polyoxometalates (POMs), at the single molecule limit using a biological nanopore-based electronic platform. The method provides a complementary approach to traditional analytical chemistry tools used in the study of these molecules.

单金属纳米粒子的高分辨率物理特性

Individual molecules can be detected and characterized by measuring the degree by which they reduce the ionic current flowing through a single ...

化学

A Closed-Type Wireless Nanopore Electrode for Analyzing Single Nanoparticles

Measuring the intrinsic features of single nanoparticles by nanoelectrochemistry holds deep fundamental importance and has potential impacts in nanoscience. However, electrochemically analyzing single nanoparticles is challenging, as the sensing nanointerface is uncontrollable. To address this challenge, we describe here the fabrication and characterization of a closed-type wireless nanopore electrode (WNE) that exhibits a highly controllable morphology and outstanding reproducibility. The facile fabrication of WNE enables the preparation of well-defined nanoelectrodes in a general chemistry laboratory without the use of a clean room and expensive equipment. One application of a 30 nm closed-type WNE in analysis of single gold nanoparticles in the mixture is also highlighted, which shows a high current resolution of 0.6 pA and high temporal resolution of 0.01 ms. Accompanied by their excellent morphology and small diameters, more potential applications of closed-type WNEs can be expanded from nanoparticle characterization to single molecule/ion detection and single-cell probing.

Here, we present a protocol for fabrication of a closed-type wireless nanopore electrode and subsequent electrochemical measurement of single nanoparticle collisions.

一种用于分析单纳米粒子的闭式无线纳米粒子电极

Measuring the intrinsic features of single nanoparticles by nanoelectrochemistry holds deep fundamental importance and has potential impacts in ...

Gold Nanoparticle Modified Carbon Fiber Microelectrodes for Enhanced Neurochemical Detection

For over 30 years, carbon-fiber microelectrodes (CFMEs) have been the standard for neurotransmitter detection. Generally, carbon fibers are aspirated into glass capillaries, pulled to a fine taper, and then sealed using an epoxy to create electrode materials that are used for fast scan cyclic voltammetry testing. The use of bare CFMEs has several limitations, though. First and foremost, the carbon fiber contains mostly basal plane carbon, which has a relatively low surface area and yields lower sensitivities than other nanomaterials. Furthermore, the graphitic carbon is limited by its temporal resolution, and its relatively low conductivity. Lastly, neurochemicals and macromolecules have been known to foul at the surface of carbon electrodes where they form non-conductive polymers that block further neurotransmitter adsorption. For this study, we modify CFMEs with gold nanoparticles to enhance neurochemical testing with fast scan cyclic voltammetry. Au3+ was electrodeposited or dipcoated from a colloidal solution onto the surface of CFMEs. Since gold is a stable and relatively inert metal, it is an ideal electrode material for analytical measurements of neurochemicals. Gold nanoparticle modified (AuNP-CFMEs) had a stability to dopamine response for over 4 h. Moreover, AuNP-CFMEs exhibit an increased sensitivity (higher peak oxidative current of the cyclic voltammograms) and faster electron transfer kinetics (lower &#916;EP or peak separation) than bare unmodified CFMEs. The development of AuNP-CFMEs provides the creation of novel electrochemical sensors for detecting fast changes in dopamine concentration and other neurochemicals at lower limits of detection. This work has vast applications for the enhancement of neurochemical measurements. The generation of gold nanoparticle modified CFMEs will be vitally important for the development of novel electrode sensors to detect neurotransmitters in vivo in rodent and other models to study neurochemical effects of drug abuse, depression, stroke, ischemia, and other behavioral and disease states.

In this study, we modify carbon-fiber microelectrodes with gold nanoparticles to enhance the sensitivity of neurotransmitter detection.

用于增强神经化学检测的金纳米粒子改性碳纤维微电极

For over 30 years, carbon-fiber microelectrodes (CFMEs) have been the standard for neurotransmitter detection. Generally, carbon fibers are aspirated into ...

Iron Nanowire Fabrication by Nano-Porous Anodized Aluminum and its Characterization

Magnetic nanowires possess unique properties that have attracted the interest of different fields of research, including basic physics, biomedicine, and data storage. We demonstrate a fabrication method for iron (Fe) nanowires&#160;via electrochemical deposition into anodic&#160;alumina oxide (AAO) templates. The templates are fabricated by anodization of aluminum (Al) discs, and the pore length and diameter are controlled by changing the anodizing conditions. Pores with an average diameter of around 120 nm are created using oxalic acid as the electrolyte. Using this method, cylindrical nanowires are synthesized, which are released by dissolving the alumina using a selective chemical etchant.

In this work, we describe a&#160;protocol to fabricate iron nanowires, including the formation of the porous alumina membrane that is used as the template, electrodeposition into templates using electrolyte solution, and the release of the nanowires into the solution.

纳米孔阳极氧化铝的铁纳米线制造及其特性

Magnetic nanowires possess unique properties that have attracted the interest of different fields of research, including basic physics, biomedicine, and ...

Preparation of Silicon Nanowire Field-effect Transistor for Chemical and Biosensing Applications

Surveillance using biomarkers is critical for the early detection, rapid intervention, and reduction in the incidence of diseases. In this study, we describe the preparation of polycrystalline silicon nanowire field-effect transistors (pSNWFETs) that serve as biosensing devices for biomarker detection. A protocol for chemical and biomolecular sensing by using pSNWFETs is presented. The pSNWFET device was demonstrated to be a promising transducer for real-time, label-free, and ultra-high-sensitivity biosensing applications. The source/drain channel conductivity of a pSNWFET is sensitive to changes in the environment around its silicon nanowire (SNW) surface. Thus, by immobilizing probes on the SNW surface, the pSNWFET can be used to detect various biotargets ranging from small molecules (dopamine) to macromolecules (DNA and proteins). Immobilizing a bioprobe on the SNW surface, which is a multistep procedure, is vital for determining the specificity of the biosensor. It is essential that every step of the immobilization procedure is correctly performed. We verified surface modifications by directly observing the shift in the electric properties of the pSNWFET following each modification step. Additionally, X-ray photoelectron spectroscopy was used to examine the surface composition following each modification. Finally, we demonstrated DNA sensing on the pSNWFET. This protocol provides step-by-step procedures for verifying bioprobe immobilization and subsequent DNA biosensing application.

We describe key steps for biosensing by using polysilicon nanowire field-effect transistors, including the preparation of the device and the immobilization and confirmation of a DNA molecular probe on the nanowire surface, as well as conditions for DNA sensing.

硅纳米线场效应晶体管的研制化学生物传感与应用

Surveillance using biomarkers is critical for the early detection, rapid intervention, and reduction in the incidence of diseases. In this study, we ...

Development of an Electrochemical DNA Biosensor to Detect a Foodborne Pathogen

Vibrio parahaemolyticus (V. parahaemolyticus) is a common foodborne pathogen that contributes to a large proportion of public health problems globally, significantly affecting the rate of human mortality and morbidity. Conventional methods for the detection of V. parahaemolyticus such as culture-based methods, immunological assays, and molecular-based methods require complicated sample handling and are time-consuming, tedious, and costly. Recently, biosensors have proven to be a promising and comprehensive detection method with the advantages of fast detection, cost-effectiveness, and practicality. This research focuses on developing a rapid method of detecting V. parahaemolyticus with high selectivity and sensitivity using the principles of DNA hybridization. In the work, characterization of synthesized polylactic acid-stabilized gold nanoparticles (PLA-AuNPs) was achieved using X-ray Diffraction (XRD), Ultraviolet-visible Spectroscopy (UV-Vis), Transmission Electron Microscopy (TEM), Field-emission Scanning Electron Microscopy (FESEM), and Cyclic Voltammetry (CV). We also carried out further testing of stability, sensitivity, and reproducibility of the PLA-AuNPs. We found that the PLA-AuNPs formed a sound structure of stabilized nanoparticles in aqueous solution. We also observed that the sensitivity improved as a result of the smaller charge transfer resistance (Rct) value and an increase of active surface area (0.41 cm2). The development of our DNA biosensor was based on modification of a screen-printed carbon electrode (SPCE) with PLA-AuNPs and using methylene blue (MB) as the redox indicator. We assessed the immobilization and hybridization events by differential pulse voltammetry (DPV). We found that complementary, non-complementary, and mismatched oligonucleotides were specifically distinguished by the fabricated biosensor. It also showed reliably sensitive detection in cross-reactivity studies against various food-borne pathogens and in the identification of V. parahaemolyticus in fresh cockles.

A protocol for the development of an electrochemical DNA biosensor comprising a polylactic acid-stabilized, gold nanoparticles-modified, screen-printed carbon electrode to detect Vibrio parahaemolyticus is presented.

电化学 DNA 生物传感器检测食源性致病菌的研究进展

Vibrio parahaemolyticus (V. parahaemolyticus) is a common foodborne pathogen that contributes to a large proportion of public health problems globally, ...