CAREER: Tunable Graphene Microdevices for Multiplexed Detection of Biomolecules Beyond Diffusion Limit

现有的和新兴的电化学生物传感器在检测生化分子方面具有很高的灵敏度、特异性和稳定性。然而，用于检测多个生物分子且灵敏度高、测量时间短的无标记、可调谐传感器(多路检测)还不成熟。该计划的目标是为设计基于石墨烯的新型生物传感器奠定基础，以生物胺类神经递质为试验床来满足这些需求。这一职业计划的研究部分将通过以下方式显著推进电化学传感领域：1)提高我们对电化学传感器设计中涉及材料-器件-读出旋钮收敛的基本问题的理解，揭示接口工程和电子门控对调谐传感器响应的影响，并阐明多模式传感和数据融合对提高准确性、特异性和可靠性的影响，以及2)利用这些知识创新一类新的可靠、多路和可调的器件。研究成果将为侧重于培训研究生和本科生，包括少数群体和代表性不足的群体的教育活动提供基础。整合了多项倡议，以增加公众对生物传感科学和技术的参与，包括为生物传感器主题课程创建新的实验室模块，为STEM中代表性不足的地区的教师举办暑期研讨会，以及为大学前女学生举办夏令营。该计划旨在通过开发新的数据融合混合液滴-石墨烯微器件，创造具有高灵敏度、高特异度和快速反应的可调和多路复用的电化学生物传感器。这一职业计划整合了实验和建模研究，包括1)阐明等离子体辅助石墨烯功能化与分析物-设备界面工程之间的相关性，以提高石墨烯微器件阵列的灵敏度和调整专一性；2)开发基于学习的多模式电化学系统，用于生物分析物的可靠分类和多路复用；3)了解时间演变系统中灵敏度与响应时间的基本极限；4)阐明电门控作为原位旋钮的基本机制，以调节石墨烯-分析物界面的反应动力学，从而实现传感器响应；以及5)通过研究广泛的药物筛选神经分泌细胞模型演示该系统的应用。该项目预计将对生物传感器工程产生长期影响，通过阐明接口和设备工程如何影响时间演化电化学系统中的检测极限和响应时间，以及多模式读数的融合如何显著提高无标记诊断的准确性、特异性和可靠性。此外，这些成果将促进2D材料功能化和设备在诊断学、生物电子学和生命科学中不断增长的领域的利用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Existing and emerging electrochemical biosensors can achieve high sensitivity, specificity, and stability in detecting biochemical molecules. However, label-free and tunable sensors for detecting multiple biomolecules (multiplexed detection) with high sensitivity and short measurement time are still beyond maturity. The goal of this program is to lay the foundations for engineering novel graphene-based biosensors to address these needs with biogenic amine neurotransmitters as testbed. The research component of this CAREER program will significantly advance the field of electrochemical sensing by 1) enhancing our understanding of fundamental questions involving convergence of material-device-readout knobs in design of electrochemical sensors, revealing the effect of interface engineering and electrical gating on tuning sensor response, and elucidating the impact of multimodal sensing and data fusion on enhancing accuracy, specificity, and reliability, and 2) utilizing this knowledge in innovating a new class of reliable, multiplexed, and tunable devices. The research outcomes will provide a foundation for educational activities focused on training graduate and undergraduate students, including minorities and underrepresented groups. Multiple initiatives are integrated to increase public engagement in biosensing science and technology, including creating new laboratory modules for a biosensor-themed course, a summer workshop for teachers from districts underrepresented in STEM, and a summer camp for pre-college female students.This program aims at creating tunable and multiplexed electrochemical biosensors with high sensitivity, specificity and rapid response by developing new data-fused hybrid droplet-graphene microdevices. This CAREER program integrates both experimental and modeling investigations which include 1) elucidating the correlation between plasma-assisted functionalization of graphene and analyte-device interface engineering to enhance sensitivity and tune specificity of graphene microdevice array; 2) developing a learning-based multimodal electrochemical system for reliable classification of bioanalytes and multiplexing; 3) understanding the fundamental limits of sensitivity versus response time in a time-evolving system; 4) elucidating the fundamental mechanisms for electrical gating as an in-situ knob to tune the reaction kinetics at the graphene-analyte interface and hence the sensor response; and 5) demonstrating the application of this system with a well-studied drug screening neurosecretion cell model. This project is anticipated to have a long-term impact on biosensor engineering by elucidating how interface and device engineering influence detection limit and response time in time-evolving electrochemical systems and how convergence with multimodal readout can significantly enhance accuracy, specificity, and reliability of label-free diagnostics. In addition, the outcomes will advance utilization of the growing field of 2D material functionalization and devices in diagnostics, bioelectronics, and life science.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.