Collaborative Research: Chemo-Physics and Molecular Design of In-situ Hydrogel-MXene Biosensors

合作研究：原位水凝胶-MXene生物传感器的化学物理和分子设计

• 批准号: 2320716
• 负责人: Shaoting Lin
• 金额: $ 33.58万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2320716&HistoricalAwards=false
• 关键词: Collaborative; Research; Chemo; Physics; Molecular

Colorectal cancer (CRC) has a significant global impact, affecting 2 million people worldwide and standing as the third leading cause of cancer-related deaths in the United States. Technologies that enable in-situ monitoring of biomarkers closely related to the development and progression of CRC are highly desirable for timely diagnosis, early intervention, and personalized treatment of CRC. However, the complicated chemical, biological, and mechanical factors within complex physiological environments present substantial challenges in achieving specific, sensitive, and durable early detection of CRC. With support from the Biosensing Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems and the Chemical Measurement and Imaging Program in the Division of Chemistry, the research groups of Prof. Shaoting Lin (Michigan State University), Prof. Chenglin Wu (Missouri University of Science and Technology), and Prof. Xinyue Liu (Michigan State University) aim to overcome these challenges by developing in-situ hydrogel-MXene biosensors capable of detecting low-level CRC biomarkers (e.g., carcinoembryonic antigen (CEA)) in simulated intestinal environments. The in-situ hydrogel-MXene biosensor will potentially lead to a big leap in bioelectronics, offering transformative impacts in disease diagnostics and paving the way for personalized healthcare. In addition, this project is expected to foster the development of the next-generation workforce in emerging biotechnologies through multi-institutional and interdisciplinary efforts including the integration of new topics in undergraduate courses and the promotion of STEM fields to encourage more students to engage in these areas of study.The goal of this project is to integrate selective-permeable hydrogels with MXene-based field-effect transistors for developing high-performance hydrogel-MXene biosensors that can achieve in-situ detection of low-level colorectal cancer (CRC) biomarkers (e.g., carcinoembryonic antigen (CEA)) in simulated intestinal environments while mitigating the influence of mobile ions. To achieve this, this project will leverage molecular design of reversible interaction, network topology, and fixed charge in hydrogels to modulate hydrogel-intestine interactions for selective biomolecular transport and to regulate hydrogel-MXene interactions for improved field-effect sensing performance. Specifically, this project will leverage the synergy of network elasticity and reversible interaction in hydrogels to independently modulate the transport of target and non-target biomolecules, thereby enabling selective and enhanced transport. In addition, this project will harness the combined efforts of molecular design, atomic simulation, and DFT calculation to optimize the design of network topology and fixed charge density of hydrogels, thus maximizing the Debye length, reduce the capacitance, and tune the bandgap at the hydrogel-MXene interface. Finally, this project will incorporate the explored hydrogel design principles to build a high-performing hydrogel-MXene biosensor capable of quantifying CRC biomarkers in simulated intestinal environments.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.

结直肠癌(CRC)具有重大的全球影响，影响着全球200万人，是美国癌症相关死亡的第三大原因。能够对与结直肠癌的发生和发展密切相关的生物标志物进行原位监测的技术对于结直肠癌的及时诊断、早期干预和个性化治疗是非常必要的。然而，在复杂的生理环境中，复杂的化学、生物和机械因素对实现特异、敏感和持久的结直肠癌早期检测提出了巨大的挑战。在化学、生物工程、环境与运输系统系的生物传感计划和化学系化学测量与成像计划的支持下，密歇根州立大学的林少亭教授、密苏里科技大学的吴成林教授和密歇根州立大学的刘新月教授的研究小组旨在通过开发能够在模拟肠道环境中检测低水平CRC生物标志物(例如癌胚抗原(CEA))的原位水凝胶-MXene生物传感器来克服这些挑战。原位水凝胶-MXene生物传感器可能会导致生物电子学的一次重大飞跃，在疾病诊断方面提供革命性的影响，并为个性化医疗铺平道路。此外，该项目预计将通过多机构和跨学科的努力来促进新兴生物技术的下一代劳动力的发展，包括在本科课程中整合新的主题和促进STEM领域的发展，以鼓励更多的学生从事这些领域的研究。该项目的目标是将选择性渗透性水凝胶与基于MXene的场效应晶体管相集成，以开发高性能水凝胶-MXene生物传感器，该传感器可以在模拟肠道环境中实现对低水平结直肠癌(CRC)生物标记物(例如癌胚抗原(CEA))的原位检测，同时减轻移动离子的影响。为了实现这一目标，该项目将利用水凝胶中可逆相互作用、网络拓扑和固定电荷的分子设计来调节水凝胶-肠道相互作用以进行选择性生物分子运输，并调节水凝胶-MXene相互作用以提高场效应传感性能。具体地说，该项目将利用水凝胶中网络弹性和可逆相互作用的协同作用来独立调节靶生物分子和非靶生物分子的传输，从而实现选择性和增强的传输。此外，该项目还将结合分子设计、原子模拟和密度泛函计算，优化水凝胶的网络拓扑和固定电荷密度的设计，从而最大化水凝胶的德拜长度，降低电容，并调节水凝胶-MXene界面的带隙。最后，该项目将结合探索的水凝胶设计原则来构建能够量化模拟肠道环境中的CRC生物标记物的高性能水凝胶-MXene生物传感器。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。