Cytokines are small proteins secreted by immune cells in response to pathogens/infections; therefore, these proteins can be used in diagnosing infectious diseases. For example, release of a cytokine interferon (IFN)-γ from T-cells is used for blood-based diagnosis of tuberculosis (TB). Our lab has previously developed an atpamer-based electrochemical biosensor for rapid and sensitive detection of IFN-γ. In this study, we explored the use of silicon nanowires (NWs) as a way to create nanostructured electrodes with enhanced sensitivity for IFN-γ. Si NWs were covered with gold and were further functionalized with thiolated aptamers specific for IFN-γ. Aptamer molecules were designed to form a hairpin and in addition to terminal thiol groups contained redox reporter molecules methylene blue. Binding of analyte to aptamer-modified NWs (termed here nanowire aptasensors) inhibited electron transfer from redox reporters to the electrode and caused electrochemical redox signal to decrease. In a series of experiments we demonstrate that NW aptasensors responded 3× faster and were 2× more sensitive to IFN-γ compared to standard flat electrodes. Most significantly, NW aptasensors allowed detection of IFN-γ from as few as 150 T-cells/mL while ELISA did not pick up signal from the same number of cells. One of the challenges faced by ELISA-based TB diagnostics is poor performance in patients whose T-cell numbers are low, typically HIV patients. Therefore, NW aptasensors developed here may be used in the future for more sensitive monitoring of IFN-γ responses in patients coinfected with HIV/TB.

中文翻译：

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纳米线适应传感器，用于电化学检测细胞分泌的细胞因子。

细胞因子是免疫细胞响应病原体/感染而分泌的小蛋白。因此，这些蛋白质可用于诊断传染病。例如，从T细胞释放细胞因子干扰素（IFN）-γ用于基于血液的结核病（TB）诊断。我们的实验室以前已经开发出一种基于atpamer的电化学生物传感器，用于快速，灵敏地检测IFN-γ。在这项研究中，我们探索了使用硅纳米线（NWs）作为创建对IFN-γ具有增强敏感性的纳米结构电极的方法。Si NW用金覆盖，并用对IFN-γ特异的硫醇适体进一步官能化。适体分子被设计成形成发夹，并且除末端硫醇基团外还包含氧化还原报告分子亚甲基蓝。分析物与适体修饰的NW（此处称为纳米线适体传感器）的结合抑制了电子从氧化还原报告分子转移到电极，并导致电化学氧化还原信号降低。在一系列实验中，我们证明，与标准扁平电极相比，NW aptasensors响应速度快3倍，对IFN-γ的敏感度提高2倍。最重要的是，NW aptasensors可以从低至150个T细胞/ mL中检测到IFN-γ，而ELISA却无法从相同数量的细胞中获取信号。基于ELISA的结核病诊断所面临的挑战之一是T细胞数量低的患者（通常是HIV患者）的不良表现。因此，此处开发的NW自适应传感器将来可用于对感染HIV / TB的患者进行更敏感的IFN-γ反应监测。