Rutkowska Agnieszka, Freedman Kevin, Skalkowska Justyna, Kim Min Jun, Edel Joshua B, Albrecht Tim
Department of Chemistry, Imperial College London, South Kensington , SW7 2AZ, London, United Kingdom.
Anal Chem. 2015 Feb 17;87(4):2337-44. doi: 10.1021/ac504463r. Epub 2015 Jan 29.
Solid-state nanopore devices with integrated electrodes are an important class of single-molecule biosensors, with potential applications in DNA, RNA, and protein detection and sequence analysis. Here we investigate solid-state nanopore sensors with an embedded gold film, fabricated using semiconductor processing techniques and focused ion beam milling. We characterize their geometric structure in three dimensions on the basis of experimental conductance studies and modeling as well as transmission electron microscopy imaging and tomography. We used electrodeposition to further shrink the pores to effective diameters below 10 nm and demonstrate how bipolar electrochemical coupling across the membrane can lead to significant contributions to the overall pore current and discuss its implications for nanopore sensing. Finally, we use metallized nanopores modified with homocysteine for the detection of insulin. We show that adsorption of the protein to the chemically modified nanopores slows down the translocation process to tens of milliseconds, which is orders of magnitude slower than expected for conventional electrophoretic transport.
带有集成电极的固态纳米孔器件是一类重要的单分子生物传感器，在DNA、RNA和蛋白质检测及序列分析方面具有潜在应用。在此，我们研究了采用半导体加工技术和聚焦离子束铣削制造的、嵌入金膜的固态纳米孔传感器。我们基于实验电导研究、建模以及透射电子显微镜成像和断层扫描，从三维角度表征了它们的几何结构。我们使用电沉积将孔隙进一步缩小至有效直径低于10纳米，并展示了跨膜的双极电化学耦合如何对总孔隙电流产生显著贡献，并讨论了其对纳米孔传感的影响。最后，我们使用用同型半胱氨酸修饰的金属化纳米孔来检测胰岛素。我们表明，蛋白质吸附到化学修饰的纳米孔上会使转运过程减慢至数十毫秒，这比传统电泳转运预期的速度慢几个数量级。
