Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544, USA.
Acc Chem Res. 2012 May 15;45(5):696-704. doi: 10.1021/ar2002057. Epub 2012 Jan 31.
The development of a miniaturized sensing platform tailored for sensitive and selective detection of a variety of biochemical analytes could offer transformative fundamental and technological opportunities. Due to their high surface-to-volume ratios, nanoscale materials are extremely sensitive sensors. Likewise, peptides represent robust substrates for selective recognition due to the potential for broad chemical diversity within their relatively compact size. Here we explore the possibilities of linking peptides to nanosensors for the selective detection of biochemical targets. Such systems raise a number of interesting fundamental challenges: What are the peptide sequences, and how can rational design be used to derive selective binders? What nanomaterials should be used, and what are some strategies for assembling hybrid nanosensors? What role does molecular modeling play in elucidating response mechanisms? What is the resulting performance of these sensors, in terms of sensitivity, selectivity, and response time? What are some potential applications? This Account will highlight our early attempts to address these research challenges. Specifically, we use natural peptide sequences or sequences identified from phage display as capture elements. The sensors are based on a variety of nanomaterials including nanowires, graphene, and carbon nanotubes. We couple peptides to the nanomaterial surfaces via traditional surface functionalization methods or self-assembly. Molecular modeling provides detailed insights into the hybrid nanostructure, as well as the sensor detection mechanisms. The peptide nanosensors can distinguish chemically camouflaged mixtures of vapors and detect chemical warfare agents with sensitivities as low as parts-per-billion levels. Finally, we anticipate future uses of this technology in biomedicine: for example, devices based on these sensors could detect disease from the molecular components in human breath. Overall, these results provide a novel platform for the development of highly sensitive and selective "nanoelectronic noses".
针对各种生化分析物的敏感和选择性检测,开发一种微型化传感平台,可以提供变革性的基础和技术机会。由于具有高的表面积与体积比,纳米级材料是极其敏感的传感器。同样,由于其相对紧凑的尺寸内具有广泛的化学多样性,肽代表了用于选择性识别的强大基质。在这里,我们探索了将肽与纳米传感器连接起来,用于选择性检测生化靶标的可能性。这些系统提出了许多有趣的基础挑战:肽序列是什么,如何通过合理设计来获得选择性结合物?应该使用什么纳米材料,以及一些组装混合纳米传感器的策略是什么?分子建模在阐明响应机制方面扮演什么角色?这些传感器的性能如何,包括灵敏度、选择性和响应时间?有哪些潜在的应用?本账户将重点介绍我们早期解决这些研究挑战的尝试。具体来说,我们使用天然肽序列或从噬菌体展示中鉴定的序列作为捕获元件。传感器基于各种纳米材料,包括纳米线、石墨烯和碳纳米管。我们通过传统的表面功能化方法或自组装将肽偶联到纳米材料表面。分子建模提供了对混合纳米结构以及传感器检测机制的详细了解。肽纳米传感器可以区分化学伪装的蒸气混合物,并以低至十亿分之几的灵敏度检测化学战剂。最后,我们预计这项技术在生物医学中的未来用途:例如,基于这些传感器的设备可以从人呼吸中的分子成分检测疾病。总的来说,这些结果为开发高灵敏度和选择性的“纳米电子鼻”提供了一个新的平台。