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

现有和新兴的电化学生物传感器在检测生化分子方面具有较高的灵敏度、特异性和稳定性。然而，用于检测多种生物分子的高灵敏度、短测量时间的无标记可调传感器（多路检测）仍未成熟。该计划的目标是为工程新型石墨烯生物传感器奠定基础，以生物胺神经递质为测试平台来解决这些需求。本CAREER项目的研究部分将通过以下方式显著推进电化学传感领域：1)增强我们对电化学传感器设计中涉及材料-器件-读出旋钮融合的基本问题的理解，揭示界面工程和电门控对调谐传感器响应的影响，阐明多模态传感和数据融合对提高准确性、特异性和可靠性的影响；2)利用这些知识来创新一类新的可靠、多路复用和可调谐设备。研究成果将为教育活动提供基础，重点是培训研究生和本科生，包括少数民族和代表性不足的群体。为了提高公众对生物传感科学和技术的参与，我们整合了多项举措，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夏季讲习班，以及为大学预科女生举办夏令营。该项目旨在通过开发新的数据融合混合液滴-石墨烯微器件，创建具有高灵敏度、特异性和快速响应的可调谐多路电化学生物传感器。该CAREER项目整合了实验和建模研究，包括1)阐明石墨烯等离子体辅助功能化与分析器件接口工程之间的相关性，以提高石墨烯微器件阵列的灵敏度和调谐特异性；2)开发基于学习的多模态电化学系统，用于生物分析物的可靠分类和多模态复用；3)理解时间演化系统中灵敏度与响应时间的基本界限；4)阐明电门控作为调节石墨烯-分析物界面反应动力学和传感器响应的原位旋钮的基本机制；5)通过一个研究良好的药物筛选神经分泌细胞模型来展示该系统的应用。该项目预计将对生物传感器工程产生长期影响，阐明接口和设备工程如何影响随时间变化的电化学系统中的检测极限和响应时间，以及多模态读出的收敛如何显著提高无标签诊断的准确性、特异性和可靠性。此外，研究结果将促进二维材料功能化和器件在诊断、生物电子学和生命科学领域的应用。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。

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.