Shao Ning, Wickstrom Eric, Panchapakesan Balaji
Delaware MEMS and Nanotechnology Laboratory, Department of Electrical and Computer Engineering, University of Delaware, Newark, DE 19716, USA.
Nanotechnology. 2008 Nov 19;19(46):465101. doi: 10.1088/0957-4484/19/46/465101. Epub 2008 Oct 21.
Recent reports have shown that nanoscale electronic devices can be used to detect a change in electrical properties when receptor proteins bind to their corresponding antibodies functionalized on the surface of the device, in extracts from as few as ten lysed tumor cells. We hypothesized that nanotube-antibody devices could sensitively and specifically detect entire live cancer cells. We report for the first time a single nanotube field effect transistor array, functionalized with IGF1R-specific and Her2-specific antibodies, which exhibits highly sensitive and selective sensing of live, intact MCF7 and BT474 human breast cancer cells in human blood. Those two cell lines both overexpress IGF1R and Her2, at different levels. Single or small bundle of nanotube devices that were functionalized with IGF1R-specific or Her2-specific antibodies showed 60% decreases in conductivity upon interaction with BT474 or MCF7 breast cancer cells in two µl drops of blood. Control experiments with non-specific antibodies or with MCF10A control breast cells produced a less than 5% decrease in electrical conductivity, illustrating the high sensitivity for whole cell binding by these single nanotube-antibody devices. We postulate that the free energy change due to multiple simultaneous cell-antibody binding events exerted stress along the nanotube surface, decreasing its electrical conductivity due to an increase in band gap. Because the free energy change upon cell-antibody binding, the stress exerted on the nanotube, and the change in conductivity are specific to a specific antigen-antibody interaction; these properties might be used as a fingerprint for the molecular sensing of circulating cancer cells. From optical microscopy observations during sensing, it appears that the binding of a single cell to a single nanotube field effect transistor produced the change in electrical conductivity. Thus we report a nanoscale oncometer with single cell sensitivity with a diameter 1000 times smaller than a cancer cell that functions in a drop of fresh blood.
最近的报告表明，当受体蛋白与在器件表面功能化的相应抗体结合时，纳米级电子器件可用于检测电性能的变化，即便这种变化来自少至十个裂解肿瘤细胞的提取物。我们推测，纳米管 - 抗体器件能够灵敏且特异地检测完整的活癌细胞。我们首次报道了一种用胰岛素样生长因子1受体（IGF1R）特异性抗体和人表皮生长因子受体2（Her2）特异性抗体功能化的单纳米管场效应晶体管阵列，该阵列对人血液中的活的、完整的MCF7和BT474人乳腺癌细胞表现出高度灵敏且选择性的传感能力。这两种细胞系均不同程度地过表达IGF1R和Her2。用IGF1R特异性或Her2特异性抗体功能化的单个或小束纳米管器件，在与两微升血液中的BT474或MCF7乳腺癌细胞相互作用时，电导率降低了60%。用非特异性抗体或MCF10A对照乳腺细胞进行的对照实验，电导率降低不到5%，这说明了这些单个纳米管 - 抗体器件对全细胞结合具有高灵敏度。我们推测，多个细胞 - 抗体同时结合事件引起的自由能变化会在纳米管表面施加应力，由于带隙增加导致其电导率降低。由于细胞 - 抗体结合时的自由能变化、施加在纳米管上的应力以及电导率的变化是特定抗原 - 抗体相互作用所特有的；这些特性可能用作循环癌细胞分子传感的指纹。从传感过程中的光学显微镜观察来看，似乎单个细胞与单个纳米管场效应晶体管的结合导致了电导率的变化。因此，我们报道了一种直径比癌细胞小1000倍、在一滴新鲜血液中起作用的具有单细胞灵敏度的纳米级肿瘤计。
