An Ultrasensitive Microfluidic Biosensor Based on Vertically-Aligned MoS2 Nanolayers

利用高度敏感的二维(2D)纳米材料的下一代生物传感器可以提供卓越的分析性能，从而使快速、超灵敏的测试成为可能，用于分子诊断、环境监测和食品安全检测等领域的各种应用。原子薄单分子层二硫化钼(MoS2)作为一种新兴的类石墨烯二维纳米材料，引起了生物传感器领域的广泛关注。尽管最近在开发高性能的单层MoS2生物传感器方面取得了进展，但以前报道的器件存在制造成品率低、生物功能化具有挑战性和重复性低的问题；这些问题在很大程度上可以归因于单层MoS2的一些固有性质和制备工艺不利于生物传感器的开发。在这个项目中，我们首次提出将一种新型的MoS2纳米结构--垂直排列的MoS2纳米层(VAMN)集成到微流控场效应管(FET)生物传感器中。由于其独特的纳米结构，VAMN实现了一些以前的MoS2生物传感器所不存在的新功能，包括轻松可靠地将生物分子固定在其垂直排列的、填充的活性边缘位置上，以及通过批量微制造实现良好的可计算性。同时，所提出的FET生物传感器还将保留单层MoS2的直接带隙、对表面分子结合的超高灵敏度和快速响应等优点，因此，它可以提供显著增强的生物传感性能，包括超高的灵敏度和高的稳定性/重复性。我们的生物传感器的微流控设计还允许轻松的设备操作、多路分析和低样品消耗。作为第一个演示，我们将应用我们的FET生物传感器来快速、超灵敏地检测脑损伤蛋白标记物，以便在心脏手术期间持续监测患者的大脑状况。这项研究将提供一个基于VAMN的强大的生物传感平台，它可以在需要超高灵敏度和极短阵列时间的许多重要应用中找到应用。

Next-generation biosensors that exploit highly-sensitive, two-dimensional (2D) nanomaterials could provide superior analytical performance and thus enable rapid, ultrasensitive tests for a variety of applications in areas such as molecular diagnosis, environmental monitoring, and food safety inspection. Atomically-thin monolayer molybdenum disulfide (MoS2), as an emerging graphene-like 2D nanomaterial, has attracted significant attention from the biosensor community. Despite the recent advancement in developing high-performance monolayer MoS2 biosensors, previously reported devices suffer from low fabrication yield, challenging biofunctionalization, and low reproducibility; these issues can be largely attributed to some inherent property and preparation process of monolayer MoS2 that are not favorable in biosensor development. In this project, we propose, for the first time, to integrate a novel form of MoS2 nanostructure, vertically-aligned MoS2 nanolayers (VAMNs), into microfluidic field-effect-transistor (FET) biosensors. Because of its unique nanostructures, the VAMNs enable a few new features that do not exist in previous MoS2 biosensors, including facile and reliable covalent immobilization of biomolecules on its vertically-aligned, populated active edge sites and good computability with batch microfabrication. In the meanwhile, the proposed FET-biosensor will also retain the advantageous physical properties of monolayer MoS2 such as its direct bandgap, ultrahigh sensitivity to surface molecule binding, and fast response; therefore, it could provide significantly-enhanced biosensing performance including ultrahigh sensitivity and high stability/reproducibility. The microfluidic design of our biosensor also allows easy device operation, multiplexed assay, and low sample consumption. As the first demonstration, we will apply our FET-biosensor to rapid, ultrasensitive detection of brain injury protein markers for constant monitoring of patient brain conditions during cardiac surgery. This research will offer a powerful VAMN-based biosensing platform, which could find many important applications where ultrahigh sensitivity and very short array time are desired.