CAREER: Multiplexed and Selective Molecular Sensing Based on Raman Enhancement Through 2D Materials

非技术描述：生物化学分子的传感在包括物联网（IoT）、大数据和机器学习支持的健康监测、疾病诊断、环境监测和食品安全在内的各个领域越来越重要。理想的分子传感平台应该是高灵敏度、选择性、无标记、产生可重复的信号，并且能够同时检测多种分析物（多重性）。如今，先进的传感器可以利用电子、光学或电化学机制实现高灵敏度和高稳定性。在受体的帮助下（意味着需要分析物的先验知识），分析物的高选择性也可以实现。然而，在短的测量时间和没有先验知识的情况下，高的多重性仍然是不成熟的。在这种情况下，通过测量光散射来探测分子振动模式的拉曼光谱，由于拉曼光谱中的多峰、极窄峰和指纹峰，成为一种很有前途的方法，可以实现上述所有要求，特别是多重性和无标记性。虽然拉曼光谱的主要缺点是信号弱，但表面增强拉曼光谱已经发展到使用结构化金属衬底来调解单分子灵敏度的问题，但它受到信号不均匀性和噪声的影响。另一种选择，通过二维材料（RE2D）的拉曼增强，用二维材料取代金属衬底，这种材料只有一个原子或几个原子厚。RE2D具有显著改善的信号均匀性和低噪声，并具有可调性的优势。本项目将通过制造各种类型的二维材料衬底，将二维材料与金属衬底结合，并施加电压来调节增强，探索进一步增强RE2D技术灵敏度和多样性的基础科学和技术。研究成果也将用作研究型本科和研究生课程的教育工具。此外，该项目还将启动一项针对女研究生的指导计划，这将在宾夕法尼亚州立大学的女学生的研究、学习、工作与生活的平衡和职业发展方面广泛受益。技术描述：本项目旨在通过二维材料（RE2D）对拉曼增强的新现象产生新的基本理解，即有机分析物分子在二维材料表面上的拉曼信号增强。这一新知识将为全新的传感器家族铺平道路，这些传感器结合了许多期望的特性：高多样性，分子选择性，前所未有的信号可靠性和可调性。通过进一步将等离子体结构与二维材料相结合，可以实现高灵敏度。该项目主要围绕两个方面展开：(1)分析二维材料-分析物分子配对对RE2D的影响，以及RE2D中分子选择的可调性；(2)确定化学和电磁机制对二维等离子体集成衬底中拉曼增强的联合影响。揭示的基础科学和演示的原型设备将有效地指导设计和制造敏感和多路复用的RE2D传感器。研究成果将整合到教育和推广活动中：为基于拉曼的纳米传感器和二维材料光电子学的本科专业创建研究型课程和研究体验，培养学生的批判性思维能力，激励他们利用先进技术找到解决社会问题的方法。PI还将启动一项女性研究生指导计划，并将宾夕法尼亚州立大学的女校友导师与女研究生配对，以支持她们的长期成功。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Nontechnical Description: The sensing of biochemical molecules has growing importance in various fields including Internet of Things (IoT), big data- and machine learning-enabled health monitoring, disease diagnosis, environmental monitoring, and food safety. An ideal molecular sensing platform should be highly sensitive, selective, label-free, generating reproducible signal, and able to detect multiple analytes simultaneously (multiplexity). Nowadays, advanced sensors can achieve high sensitivity and stability using electronic, optical or electrochemical mechanisms. With the assistance of receptors (meaning prior knowledge of the analytes is required), high selectivity of analytes can also be realized. However, high multiplexity within short measurement time and without prior knowledge is still beyond maturity. In this context, Raman spectroscopy, which probes the molecular vibrational modes through the measurement of light scattering, stands out as a promising method to achieve all the above requirements, in particular multiplexity and label-free, due to the multiple, extremely narrow and fingerprinting peaks in Raman spectra. While the main drawback of Raman spectroscopy is the weak signal, surface-enhanced Raman spectroscopy has been developed to mediate this issue with even single-molecule sensitivity using structured metal substrates, yet it has suffered from signal non-uniformity and noise. An alternative, Raman enhancement through two-dimensional materials (RE2D), replaces metallic substrates with 2D materials, a type of material only one atom or a few atoms thick. RE2D has exhibited significantly improved signal uniformity and low noise with the added advantage of tunability. This project will explore the fundamental science and techniques to further enhance the sensitivity and multiplexity of RE2D technology, by fabricating various types of 2D material substrates, combining 2D materials with metallic substrates, and applying electrical voltage to tune the enhancement. The research outcome will also be used as educational tools for research-like undergraduate and graduate courses. In addition, the PI will initiate a mentoring program for female graduate students, which will broadly benefit Penn State female students in their research, study, work-life balance and career development. Technical Description: This project aims to generate new fundamental understanding of the novel phenomenon of Raman enhancement through two-dimensional materials (RE2D), i.e. the enhancement of Raman signals of organic analyte molecules when placed on 2D material surfaces. This new knowledge will pave the way for an entirely new family of sensors that combine a number of desired features: high multiplexity, molecular selectivity, unprecedented signal reliability, and tunability. By further integrating plasmonic structures with 2D materials, high sensitivity will be achieved. The project is organized around two main thrusts: (1) analysis of the effects of 2D material-analyte molecule pairing on RE2D, as well as the tunability of molecular selection in RE2D; and (2) determination of the combined effects of chemical and electromagnetic mechanisms on Raman enhancement in a 2D-plasmonic integrated substrate. The fundamental science revealed and the prototype devices demonstrated will effectively guide the design and fabrication of sensitive and multiplexed RE2D sensors. The research outcomes will be integrated into the education and outreach activities: creating research-like courses and Research Experience for Undergraduate programs on Raman-based nanosensors and 2D material optoelectronics, which cultivate students’ abilities of critical thinking and motivate them to find solutions to societal problems using advanced technologies. The PI will also initiate a women graduate student mentoring program, and pair female Penn State alumnae mentors with female graduate students to support their long-term success.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.